Skip to main content

Main menu

  • Online first
    • Online first
  • Current issue
    • Current issue
  • Archive
    • Archive
  • Submit a paper
    • Online submission site
    • Information for authors
  • About the journal
    • About the journal
    • Editorial board
    • Information for authors
    • FAQs
    • Thank you to our reviewers
      • Thank you to our reviewers
    • American Federation for Medical Research
  • Help
    • Contact us
    • Feedback form
    • Reprints
    • Permissions
    • Advertising
  • BMJ Journals

User menu

  • Login

Search

  • Advanced search
  • BMJ Journals
  • Login
  • Facebook
  • Twitter
JIM

Advanced Search

  • Online first
    • Online first
  • Current issue
    • Current issue
  • Archive
    • Archive
  • Submit a paper
    • Online submission site
    • Information for authors
  • About the journal
    • About the journal
    • Editorial board
    • Information for authors
    • FAQs
    • Thank you to our reviewers
    • American Federation for Medical Research
  • Help
    • Contact us
    • Feedback form
    • Reprints
    • Permissions
    • Advertising

Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68

Mohammad Amin Momeni-Moghaddam, Gholamreza Asadikaram, Mohammad Masoumi, Erfan Sadeghi, Hamed Akbari, Moslem Abolhassani, Alireza Farsinejad, Morteza Khaleghi, Mohammad Hadi Nematollahi, Shahriar Dabiri, Mohammad Kazemi Arababadi
DOI: 10.1136/jim-2021-001935 Published 1 December 2022
Mohammad Amin Momeni-Moghaddam
1 Nutrition and Biochemistry, Gonabad University of Medical Sciences, Gonabad, Iran (the Islamic Republic of)
2 Department of Clinical Biochemistry, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran (the Islamic Republic of)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mohammad Amin Momeni-Moghaddam
Gholamreza Asadikaram
2 Department of Clinical Biochemistry, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran (the Islamic Republic of)
3 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran (the Islamic Republic of)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Gholamreza Asadikaram
Mohammad Masoumi
4 Cardiovascular Research Center, Institute of Basic and Clinical ‎Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erfan Sadeghi
5 Fasa University of Medical Sciences, Fasa, Iran (the Islamic Republic of)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hamed Akbari
6 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Moslem Abolhassani
7 Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences,Kerman University of Medical Sciences, Kerman, Iran
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alireza Farsinejad
8 Pathology and Stem Cell Research Center, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Morteza Khaleghi
8 Pathology and Stem Cell Research Center, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mohammad Hadi Nematollahi
9 Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mohammad Hadi Nematollahi
Shahriar Dabiri
8 Pathology and Stem Cell Research Center, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mohammad Kazemi Arababadi
10 Rafsanjan University of Medical Sciences, Rafsanjan, Iran (the Islamic Republic of)
11 Department of Laboratory Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran (the Islamic Republic of)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • eLetters
  • Info & Metrics
  • PDF
Loading

Abstract

The molecular mechanisms of opium with regard to coronary artery disease (CAD) have not yet been determined. The aim of the present study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in patients with CAD with and without opium addiction. This case–control study was conducted in three groups: (1) opium-addicted patients with CAD (CAD+OA, n=30); (2) patients with CAD with no opium addiction (CAD, n=30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n=17). Protein and messenger RNA (mRNA) levels of CD9, CD36, and CD68 were evaluated by flow cytometry and reverse transcription-quantitative PCR methods, respectively. Consumption of atorvastatin, aspirin, and glyceryl trinitrate was found to be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD+OA group than in the CAD and Ctrl groups (p=0.001 and p=0.005, respectively). MDA levels significantly increased in the CAD and CAD+OA groups in comparison with the Ctrl group (p=0.010 and p=0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at the gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Significance of this study

What is already known about this subject?

  • The molecular mechanism of opium with regard to coronary artery disease (CAD) has not yet been determined.

  • Opium-induced oxidation may alter the expression of the scavenger receptors and their regulatory factors.

  • Oxidative stress may affect nitric oxide production, which has contradictory roles in relation to cardiovascular diseases.

What are the new findings?

  • The findings showed that the plasma level of tumor necrosis factor alpha rose significantly in opium-addicted patients with CAD in comparison with the CAD and control groups.

  • It was found that opium did not affect the expression of CD9, CD36, and CD68 receptors in patients with CAD.

  • The results also demonstrated that opium did not affect the plasma levels of malondialdehyde, interferon gamma, and nitric oxide metabolites in patients with CAD.

How might these results change the focus of research or clinical practice?

  • Further large-scale studies are needed to reveal the exact mechanisms and effects of opium and routine medications on the expression of CD9, CD36, and CD68 receptors in patients with CAD.

Introduction

Coronary artery disease (CAD) is considered one of the main causes of death around the globe.1 One of the known factors that can lead to CAD is atherosclerosis,2 3 which is caused by chronic inflammation and plaque formation in medium-sized to large-sized arteries.4 Various risk factors are involved in the development of atherosclerotic plaques, including arterial hypertension, smoking, lifestyle, high-fat diet, physical inactivity, and diabetes.5–7 Moreover, studies have shown that opium consumption may have destructive effects on atherosclerotic plaque formation.8 9 Another factor that plays a role in plaque formation is oxidized low-density lipoprotein (ox-LDL).4 Macrophages take up ox-LDL via scavenger receptors, such as CD68 and CD36. It has been demonstrated that either CD36 or CD68 plays a critical role in the pathogenesis of CAD and its complications such as atherosclerosis.10 Scavenger receptors act through various signaling pathways and perform their function via interactions with other receptors, such as integrins, Toll-like receptors, and tetraspanins.10 11 CD9, which is a member of the tetraspanin family, is expressed on various cells, such as platelets and macrophages. It has been shown that this important molecule can interfere with the functions of the scavenger receptors on macrophages, and the genetic deletion of CD9 leads to a decrease in CD36 signaling in response to ox-LDL and a reduction in foam cell generation.12 Thus, it is hypothesized that CD9 may affect the pathogenesis of atherosclerosis and CAD in a scavenger receptor-dependent manner. However, the altered expression of these receptors, including scavenger receptors and CD9, by direct or indirect risk factors, may change monocyte functions.

Opium, as a narcotic drug, may interfere with CAD.13 The molecular mechanism of action of this substance with regard to this disease has not yet been determined. In some societies such as in Asian communities, the traditional belief among people is that opium might have a positive effect on cardiovascular health and diabetes, hypertension, and dyslipidemia.14 Studies have shown that using opium has a direct correlation with incidence of cardiovascular diseases (CVDs) and increases the risk of inflammation and oxidative stress, which both contribute to the development of atherosclerotic plaques.13 For example, the expression of CD36 in macrophages was enhanced as a result of oxidative stress, thereby increasing the absorption of ox-LDL.15 Therefore, the oxidation induced by opium may alter the expression of scavenger receptors and their regulatory factors. Moreover, oxidative stress affects lipids and leads to the generation of secondary compounds, such as malondialdehyde (MDA), as a result of the peroxidation of polyunsaturated fatty acids.16 17 In addition, oxidative stress may also affect nitric oxide (NO) production, which has contradictory roles in relation to CVD.18

The present study aimed to evaluate the expression of CD9, CD36, and CD68 on the monocytes of patients with CAD with and without opium addiction at both the messenger RNA (mRNA) and protein levels. Moreover, the plasma levels of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), as proinflammatory cytokines, and MDA and nitric oxide metabolites (NOx), as oxidative stress markers, were compared between the studied groups.

Materials and methods

Subjects

As a case–control study, the present research was carried out on a total of 77 individuals with suspected CAD who were considered candidates for coronary angiography and were referred to Shafa Hospital of Kerman University of Medical Sciences, Kerman, Iran (from July 2017 to February 2018). Coronary angiography was performed on all the subjects. Some of the subjects in the research were under treatment with drugs such as atorvastatin, glyceryl trinitrate, aspirin, clopidogrel, bisoprolol, valsartan, metoprolol, captopril, carvedilol, isosorbide, and losartan. The inclusion criteria were as follows: men with symptoms of ischemic heart disease and those diagnosed with CAD by coronary angiography. The exclusion criteria included patients with a history of cancer, diabetes, autoimmune and respiratory diseases, cerebral infarction, and use of alcohol, cigarettes, methadone, and other opiates, such as morphine, heroin, and similar narcotics. All opium-addicted patients used opium more than 500 mg daily for at least 1 year before sample collection. Subjects were sorted into three groups: (1) severe CAD (stenosis >50%) and opium-addicted (CAD+OA, n=30); (2) severe CAD (stenosis >50%) with no opium addiction (CAD, n=30); and (3) normal coronary arteries with no opium addiction as the control group (Ctrl, n=17).

Samples and data collection

Demographic information was collected through interviews with the subjects. Body mass index was computed as the ratio of weight to the square of height. About 10 mL of blood were drawn from subjects after overnight fasting (collected before breakfast at 08:00) and poured into two separate tubes containing EDTA. One tube was centrifuged (10 min at 3000 revolutions per minute (RPM)) and plasma was separated and then kept at −70°C for measurement of biochemical parameters, TNF-α, IFN-γ, NOx, and MDA. The other tube was used for monocyte separation, evaluation of cell surface CD36, CD68, and CD9, and extraction of total mRNA as described in the following sections. Based on a previous article19 and using the following formula, the minimum sample size for the comparison of IFN-γ between the study groups, considering α=0.05, β=0.2, d=48.89, and effect size (ES)=0.983, was calculated to be 18 subjects in each group.

Embedded Image

Biochemistry factors

The plasma levels of fasting plasma glucose, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-c), creatinine, and urea were determined using standard kits (Pars Azmoon, Tehran, Iran) and an autoanalyzer (Roche Hitachi 911) in a standard laboratory context. Additionally, low-density lipoprotein cholesterol (LDL-c) was calculated using the Friedewald equation. Plasma sodium and potassium levels were measured via an ion-selective electrode.20

Separation of monocytes

First, isolation of peripheral blood mononuclear cells (PBMCs) was performed from anticoagulated blood by density gradient centrifugation using Ficoll histopaque. Subsequently, PBMCs were incubated with anti-human CD14 magnetic particles (catalog number: 557769; BD Biosciences, USA) at room temperature for 50 min, and then the monocytes were isolated by the cell separation magnet (catalog number: 552311; BD Biosciences).

Analysis of CD9, CD36, and CD68 mRNA expression

To evaluate mRNA expression, reverse transcription-quantitative PCR (RT-qPCR) was performed. Briefly, RNA was extracted from monocytes by total RNA extraction solution (catalog number: K-3090; Bioneer, Daejeon, South Korea) and purified RNA was qualitatively and quantitatively assessed using a NanoDrop spectrophotometer (ND-1000; Thermo Fisher Scientific, Wilmington, USA). In addition, complementary DNA (cDNA) was synthesized via the reverse transcription system by the cDNA Synthesis Kit (catalog number: 6110A; Takara Bio, California, USA). The primers used for amplification of CD9, CD36, and CD68 are listed in online supplemental table S1. Beta-actin was used as the housekeeping gene. Moreover, RT-qPCR was performed using RealQ Plus Master Mix Green (catalog number: 4324402; Amplicon, Odense, Denmark) in a real-time PCR machine (Mic, Australia) according to the following program: the CD9 gene was initially denatured for 15 min at 95°C, followed by 35 cycles of denaturation (20 s) at 95°C, annealing (20 s) at 69°C, extension (20 s) at 72°C, along with a final extension at 72°C for 5 min. RT-qPCR for CD36, CD68, and beta-actin was performed as follows: initial denaturation for 15 min at 95°C, followed by 40 cycles of denaturation (30 s) at 95°C, annealing (60 s), extension (35 s) at 60°C, and the final extension for 5 min at 72°C. The expressions of these molecules were computed using the 2–ΔΔCT formula.21

Supplementary data

[jim-2021-001935supp001.pdf]

Flow cytometry analysis

To detect CD9, CD36, and CD68 on monocytes, PBMCs were fixed with a fixation solution (catalog number: 420801; BioLegend, San Diego, USA) and incubated at room temperature in darkness for 20 min. They were then centrifuged and the diluted intracellular staining permeabilization wash buffer (catalog number: 421002; BioLegend) was added to the cellular deposition and centrifuged (the process was repeated twice). After centrifugation, the cells were washed with phosphate-buffered saline (PBS). PBMCs were stained using the antibodies listed in online supplemental table S2. Anti-human CD14 was used to identify monocytes. Approximately 10,000 stained cells were evaluated using a flow cytometry instrument (catalog number: 342976; BD FACSCalibur, USA).

Measuring cytokine levels

Plasma levels of IFN-γ and TNF-α were evaluated using commercially available ELISA kits (Karmania Pars Gene Company, Kerman, Iran) according to the manufacturer’s instruction.

MDA measurement

One of the substances measured as a lipid peroxidation index is MDA. The measurement of this compound was conducted by the thiobarbituric acid (TBA) assay protocol. In this method, in the presence of the trichloroacetic acid-TBA-hydrochloric acid reagent, MDA reacts with TBA and produces a pink color whose final absorbance was measured at 535 nm.22 23

Evaluation of NOx

Due to the short half-life of NO in the blood, its stable metabolites (NOx), nitrite (NO2 −), and nitrate (NO3 −) were detected by the Griess method.24 25 First, using ZnSO4 and in the presence of 0.3 M NaOH, plasma deproteinization was performed. Then vanadium (III) chloride (VaCl3) (for converting nitrate into nitrite) and the Griess reagent (2% sulfanilamide in 5% phosphoric acid and 0.1% NEDD (N-(1-naphthyl) ethylenediamine dihydrochloride) in deionized water) were added to the deproteinized plasma and incubated at 37°C for 30 min. Finally, the optical density was measured at 540 nm.26

Statistical analysis

Continuous and categorical variables are presented as mean and SEM or number and percentage. In addition, one-way analysis of variance (ANOVA) and χ2 test were used to compare the variables between the study groups. One-way ANOVA followed by the Bonferroni test was applied for pairwise comparison of log(y) between the study groups using the logarithm function as the transforming method for normalizing the response variables. All analyses were performed in SPSS V.24, and the significance level was set at 0.05.

Results

Demographic analysis

Table 1 presents the subjects’ demographic and clinical characteristics. There were significant differences in age, TC, HDL-c, and LDL-c between the three groups (p=0.028, p=0.003, p<0.001, and p=0.009, respectively). However, no significant differences were observed with regard to other variables (p>0.05 for all comparisons).

View this table:
  • View inline
  • View popup
Table 1

Demographic and biochemical parameters of subjects in the three groups

Comparison of drug usage

Comparisons of drug consumption between the three studied groups are depicted in online supplemental table S3. Significant differences were found in the consumption of aspirin (p=0.015), glyceryl trinitrate (p=0.006), atorvastatin (p=0.008), and clopidogrel (p=0.012) between the three studied groups before coronary angiography. However, the analysis did not reveal any significant differences in the consumption of other drugs between the three studied groups (p>0.05 for all comparisons).

Plasma levels of TNF-α, IFN-γ, MDA, and NOx

Comparisons of the mean plasma levels of TNF-α, IFN-γ, MDA, and NOx between the groups are presented in table 2. The plasma level of TNF-α was significantly higher in the CAD +OA group than in the CAD and Ctrl groups (p=0.001 and p=0.005, respectively). However, no significant differences were observed between patients with CAD and the Ctrl group (p>0.05 for both comparisons). MDA plasma levels significantly increased in the CAD and CAD +OA groups in comparison with the Ctrl group (p=0.010 and p=0.002, respectively). However, no significant difference was observed between the CAD +OA group and the CAD group (p>0.05 for both comparisons). In addition, there was no significant difference regarding the mean level of IFN-γ and NOx between the studied groups (p>0.05 for both comparisons).

View this table:
  • View inline
  • View popup
Table 2

Pairwise comparison using one-way ANOVA followed by Bonferroni test

Gene expression of cluster of differentiation (CD) markers

Figure 1 and table 3 demonstrate the comparison of the mean levels of CD9, CD36, and CD68 mRNA expression in the CAD +OA, CAD, and Ctrl groups. The analysis did not reveal any significant difference in CD9, CD36, and CD68 mRNA expression in two-by-two comparisons between the study groups (p>0.05 for all comparisons).

View this table:
  • View inline
  • View popup
Table 3

Comparison of CD9, CD36, and CD68 mRNA expression between the CAD+OA, CAD, and Ctrl groups

Figure 1
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1

CD9, CD36, and CD68 mRNA expression levels in the CAD+OA, CAD, and Ctrl groups. (A) No statistically significant difference was found in the CD9 mRNA expression level between the three study groups (p>0.05 for all comparisons). (B) No significant difference was found in the CD36 mRNA expression level between the three study groups. (C) No significant difference was found in the CD68 mRNA expression level between the three study groups (p>0.05 for all comparisons). CAD, coronary artery disease; CAD+OA, coronary artery disease and opium addiction; Ctrl, control.

Protein level of CD markers

Figure 2 and table 4 show the comparison of the mean levels of CD9, CD36, and CD68 proteins in the CAD +OA, CAD, and Ctrl groups. No significant differences were observed in terms of CD9, CD36, and CD68 proteins between the three study groups (p>0.05 for all comparisons).

View this table:
  • View inline
  • View popup
Table 4

Comparison of CD9, CD36, and CD68 protein levels between the CAD+OA, CAD, and Ctrl groups

Figure 2
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2

CD9, CD36, and CD68 protein levels in the CAD+OA, CAD, and Ctrl groups. (A) There was no significant difference in the CD9 protein level between the three study groups (p>0.05 for all comparisons). (B) No significant difference was found in the CD36 protein level between the three study groups (p>0.05 for all comparisons). (C) There was no significant difference in the CD68 protein level between the three groups (p>0.05 for all comparisons). CAD, coronary artery disease; CAD+OA, coronary artery disease and opium addiction; Ctrl, control.

Discussion

The findings of the current study indicated that the plasma level of TNF-α rose significantly in the CAD +OA group in comparison with the CAD and Ctrl groups. However, the results indicated that opium did not affect the expression of CD9, CD36, and CD68 receptors and the plasma levels of MDA, IFN-γ, and NOx in patients with CAD.

We found that consumption of atorvastatin, clopidogrel, aspirin, and glyceryl trinitrate was significantly higher in the CAD+OA and CAD groups in comparison with the control group. Given the anti-inflammatory effect of these drugs, the plasma levels of TNF-α were not significantly different in patients with CAD compared with the control group. However, in the CAD+OA group, the plasma levels were significantly higher than in the CAD and control groups. By affecting endothelial cells, triggering growth factors and chemoattractants, and interfering with the thrombotic process, TNF-α assists in the development of CAD.27 With respect to the effects of opium on TNF-α, Yarahmadzehi et al 28 revealed that this cytokine was increased in the brain tissue of opium-treated rats. A study conducted by Zhao et al 29 indicated that atorvastatin reduced the serum levels of TNF-α in hypercholesterolemic rabbits compared with controls. In another research conducted by McFarland et al,30 it was demonstrated that statins could decrease TNF-α secretion from the Tohoku Hospital Pediatrics-1 (THP-1) cell line. Furthermore, Al-Bahrani et al 31 found that aspirin and clopidogrel decreased the production of TNF-α in the leukocytes of patients who had acute stroke. On the other hand, it has been hypothesized that opium may modulate the production of cytokines by affecting the immune system cells.17 Although reports about the effects of opium on the immune system are limited, there are numerous studies on the impact of opium derivatives, namely morphine, on the immune system, showing that morphine can induce oxidative stress.32 Sawaya et al 33 indicated that morphine enhanced the expression of TNF-α in U937, astrocytes, and microglia, and such an increase may be mediated by the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Moreover, Peng et al 34 reported that mice treated with morphine exhibited an enhanced mRNA expression of TNF-α. Therefore, prior studies confirm our hypothesis that opium may be involved in the development of CAD through its effect on the immune system and increasing TNF-α, which is a proinflammatory cytokine. Although the plasma levels of IFN-γ, a proinflammatory cytokine, were higher in the CAD+OA group than the other two groups, the difference between the three groups was not significant. Because IFN-γ is found in high amounts in the atherosclerotic plaque areas,35–37 and since our subjects received anti-inflammatory drugs, the level of this cytokine in the CAD groups was not significantly different from that in the control group. Enayati et al 38 showed that the expression of IFN-γ in PBMCs of patients with CAD was not significantly different from that of the control group.

The crucial roles played by the scavenger receptors and the upregulation of the molecules in patients with CAD have been documented previously.39 40 However, it was observed that mRNA or protein levels of CD36 and CD68, as the scavenger receptors of macrophages, and CD9, as a family member of tetraspanins, did not alter in the studied groups. Thus, according to the present results, it seems that treatment of both CAD and CAD +OA patients with atorvastatin, clopidogrel, aspirin, and glyceryl trinitrate regulated the expression of scavenger receptors independent of opium. Previous in vivo studies have also shown that inflammation increases the expression of CD68 as a scavenger receptor.41 Since CAD +OA patients and patients with CAD without opium addiction were taking aspirin, this drug reduced inflammation,42 and consequently the expression of CD68 did not change in monocytes. The findings of a study performed on the human macrophage THP-1 cell line treated with opium were consistent with our results, showing that no significant differences were found in the expression of CD36, CD68, and CD9 at the gene and protein levels.43 As described previously, CD9 is a family member of tetraspanins that is capable of altering the function of scavenger receptors.44 In a study on mice, it was shown that CD9 is associated with CD36 at the macrophage level and contributes to the uptake of ox-LDL via CD36. Moreover, in mice lacking the CD9 gene, lipid accumulation in macrophages was decreased and consequently reduced foam cell formation.44 Furthermore, it has been shown that CD9 expression is reduced in macrophages due to the effect of lipopolysaccharides (LPS), as inflammatory promoter molecules, and a decrease in the amount of tetraspanin may contribute to the progression of inflammatory diseases. In addition, statins were shown to decrease lung inflammation in mice by increasing macrophage CD9 expression.45 Therefore, due to the contradictory results, the precise role and function of CD9 in relation to CAD and opium require further investigation.

Given the fact that oxidative stress is involved in CVD development, it can be concluded that oxidative stress is the main cause of MDA production.46 The current study demonstrated that MDA serum levels significantly increased in CAD or CAD +OA patients; hence, it may be deduced that oxidative stress affects CAD and CAD +OA patients. In an in vivo study, the serum MDA level was higher in rats that received opium than in the control group.47 Some studies examined MDA levels in patients with CAD and normal individuals. It was shown that the level of MDA in subjects with CAD was nearly twofold higher.48 49 Thus, our results confirmed the impact of both CAD and addiction to opium on the MDA levels. However, there were no significant differences between CAD and CAD +OA patients, implying that opium addiction does not have synergistic effects with CAD to increase the levels of MDA.

It is believed that NO may have different effects on the cardiovascular system, depending on the isoform that is produced. Studies have shown that reactive oxygen species can react with NO to produce peroxynitrite (ONOO−), thereby reducing NO levels and producing another free radical to cause further damage to cellular components.50 NO has been implicated in the maintenance of tissue perfusion, protection against LPS-derived toxic lipids, and maintenance of red blood cells in septicemia.51 In general, it can be said that NO has a dual role in the body, and in addition to its physiological function it can play a pathological role. In a study carried out on opium addicts, the circulating NO level was higher in addicts than in the control group, but the difference was not significant.52 In another study on subjects with CAD, the mean plasma NO levels were lower than those in the control group.53 In the study by Kalantarian et al,54 there was no significant difference between serum NO levels in subjects with CAD and the control group. In contrast to those studies, in another investigation, NO was found to be higher in patients with CAD than in the control group.55 In the present study, opium did not affect the NOx plasma levels. The NO level was higher in the CAD+OA group than in the Ctrl group even though there was no statistically significant difference. It is assumed that different diets, medications, blood pressure, and the presence or absence of other factors which are not included are effective in oxidative stress and the NO level may be the possible cause of these discrepancies.56

Various studies have shown that opium has different and contradictory effects (as a potential risk/protective/impartial factor) on CVD. A population-based study by Sadeghian et al 57 revealed that using opium was a risk factor for CAD, excluding cigarette smokers, and they reported the same general findings. However, a study carried out on 460 patients with myocardial infarction showed that the inpatient mortality rate was lower in opium users. Even though this difference was not significant, among patients with anterior wall infarction, the mortality rate was significantly higher in non-opium users.58 On the other hand, a study conducted by Sharafi et al 59 assessing 1-year major adverse cardiac events in 1545 patients did not show a significant difference between patients with and without opium use disorder. Similarly, Roohafza et al 60 claimed that the initial death rate was similar between opium users and non-users.

A number of limitations must be considered when interpreting the present results. These limitations include the fact that it was difficult and time-consuming to select the Ctrl group subjects out of all the candidates for coronary angiography without any criticism of coronary vessel stenosis, as well as to choose the CAD +OA group out of patients who were addicted to opium but did not consume cigarettes. Nevertheless, the current research has several advantages as well. In addition to these novel findings, this investigation evaluated the association between opium addiction, excluding cigarette use, and CAD development and routine medications. Furthermore, in the present study, CAD diagnosis was carried out by coronary angiogram in all the subjects, whereas some other studies identified CAD by an ECG or a thallium scan.

Conclusions

The findings showed that opium might increase inflammation in the body by increasing the plasma levels of TNF-α, a proinflammatory cytokine, and interfering with anti-inflammatory drugs, and thus opium may be involved in the development of CVD. In addition, the findings revealed that opium did not show a significant effect on the expression of CD36, CD68, and CD9 at the gene and protein levels, which can be due to the consumption of antiplatelets and statins. However, it may be involved in the development of CAD by inducing inflammation through other pathways. Nevertheless, further large-scale studies are needed to reveal the exact mechanism and effects of opium and routine medications on the expression of these genes.

Data availability statement

Data are available upon reasonable request.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).

Ethics approval

This study abided by the Declaration of Helsinki in regard to research involving human subjects and was approved by the Ethics Committee of Kerman University of Medical Sciences, Kerman, Iran (IR.KMU.REC.95.261).

Acknowledgments

This work was part of a PhD thesis. The authors gratefully acknowledge the financial support of the Kerman University of Medical Sciences and would like to thank all the subjects in the study.

Footnotes

  • Contributors MA-MM, GA, and MK set up the study design and interpretation of the data. MA-MM, GA, ES, and HA performed statistical analyses, interpretation of the data, and original draft preparation. GA, HA, and MA-MM revised manuscript critically and provide of continuous guidance throughout the study. MA-MM, MA, MHN, AF, MK, and SD collection of data and performing the experiments. All authors read and approved the final manuscript. GA is responsible for the overall content as the guarantor.

  • Funding This work was supported by a grant from the Kerman University of Medical Sciences (IR/KMU/95/212).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

References

  1. ↵
    1. Mastoi Q-U-A ,
    2. Wah TY ,
    3. Gopal Raj R ,
    4. Iqbal U , et al
    . Automated diagnosis of coronary artery disease: a review and workflow. Cardiol Res Pract 2018;2018:2016282.doi:10.1155/2018/2016282 pmid:http://www.ncbi.nlm.nih.gov/pubmed/29507812
    OpenUrlPubMed
  2. ↵
    1. Akbari H ,
    2. Asadikaram G ,
    3. Vakili S , et al
    . Atorvastatin and losartan may upregulate renalase activity in hypertension but not coronary artery diseases: the role of gene polymorphism. J Cell Biochem 2019;120:9159–71.doi:10.1002/jcb.28191 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30548657
    OpenUrlPubMed
  3. ↵
    1. Riccioni G ,
    2. Sblendorio V
    . Atherosclerosis: from biology to pharmacological treatment. J Geriatr Cardiol 2012;9:305.doi:10.3724/SP.J.1263.2012.02132 pmid:http://www.ncbi.nlm.nih.gov/pubmed/23097661
    OpenUrlCrossRefPubMed
  4. ↵
    1. Gisterå A ,
    2. Hansson GK
    . The immunology of atherosclerosis. Nat Rev Nephrol 2017;13:368–80.doi:10.1038/nrneph.2017.51 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28392564
    OpenUrlPubMed
  5. ↵
    1. Wolf D ,
    2. Stachon P ,
    3. Bode C , et al
    . Inflammatory mechanisms in atherosclerosis. Hämostaseologie 2014;34:63–71.doi:10.5482/HAMO-13-09-0050
    OpenUrl
  6. ↵
    1. Masoumi M ,
    2. Shahesmaeili A ,
    3. Mirzazadeh A , et al
    . Opium addiction and severity of coronary artery disease: a case-control study. J Res Med Sci 2010;15:27.pmid:http://www.ncbi.nlm.nih.gov/pubmed/21526055
    OpenUrlPubMed
  7. ↵
    1. Hosseini SK ,
    2. Masoudkabir F ,
    3. Vasheghani-Farahani A , et al
    . Opium consumption and coronary atherosclerosis in diabetic patients: a propensity score-matched study. Planta Med 2011;77:1870–5.doi:10.1055/s-0031-1280017 pmid:http://www.ncbi.nlm.nih.gov/pubmed/21800277
    OpenUrlPubMedWeb of Science
  8. ↵
    1. Mohammadi A ,
    2. Darabi M ,
    3. Nasry M , et al
    . Effect of opium addiction on lipid profile and atherosclerosis formation in hypercholesterolemic rabbits. Exp Toxicol Pathol 2009;61:145–9.doi:10.1016/j.etp.2008.08.001 pmid:http://www.ncbi.nlm.nih.gov/pubmed/18838257
    OpenUrlPubMed
  9. ↵
    1. Esmaeili Nadimi A ,
    2. Pour Amiri F ,
    3. Sheikh Fathollahi M , et al
    . Opium addiction as an independent risk factor for coronary microvascular dysfunction: a case-control study of 250 consecutive patients with slow-flow angina. Int J Cardiol 2016;219:301–7.doi:10.1016/j.ijcard.2016.06.034 pmid:http://www.ncbi.nlm.nih.gov/pubmed/27343424
    OpenUrlPubMed
  10. ↵
    1. Park YM
    . CD36, a scavenger receptor implicated in atherosclerosis. Exp Mol Med 2014;46:e99.doi:10.1038/emm.2014.38 pmid:http://www.ncbi.nlm.nih.gov/pubmed/24903227
    OpenUrlCrossRefPubMed
  11. ↵
    1. Gottfried E ,
    2. Kunz-Schughart LA ,
    3. Weber A , et al
    . Expression of CD68 in non-myeloid cell types. Scand J Immunol 2008;67:453–63.doi:10.1111/j.1365-3083.2008.02091.x pmid:http://www.ncbi.nlm.nih.gov/pubmed/18405323
    OpenUrlCrossRefPubMedWeb of Science
  12. ↵
    1. Huang W ,
    2. Febbraio M ,
    3. Silverstein RL
    . CD9 tetraspanin interacts with CD36 on the surface of macrophages: a possible regulatory influence on uptake of oxidized low density lipoprotein. PLoS One 2011;6:e29092.doi:10.1371/journal.pone.0029092
  13. ↵
    1. Masoudkabir F ,
    2. Sarrafzadegan N ,
    3. Eisenberg MJ
    . Effects of opium consumption on cardiometabolic diseases. Nat Rev Cardiol 2013;10:733–40.doi:10.1038/nrcardio.2013.159 pmid:http://www.ncbi.nlm.nih.gov/pubmed/24145895
    OpenUrlCrossRefPubMed
  14. ↵
    1. Karam GA ,
    2. Reisi M ,
    3. Kaseb AA , et al
    . Effects of opium addiction on some serum factors in addicts with non-insulin-dependent diabetes mellitus. Addict Biol 2004;9:53–8.doi:10.1080/13556210410001674095 pmid:http://www.ncbi.nlm.nih.gov/pubmed/15203439
    OpenUrlCrossRefPubMed
  15. ↵
    1. Fuhrman B ,
    2. Volkova N ,
    3. Aviram M
    . Oxidative stress increases the expression of the CD36 scavenger receptor and the cellular uptake of oxidized low-density lipoprotein in macrophages from atherosclerotic mice: protective role of antioxidants and of paraoxonase. Atherosclerosis 2002;161:307–16.doi:10.1016/S0021-9150(01)00646-3 pmid:http://www.ncbi.nlm.nih.gov/pubmed/11888513
    OpenUrlCrossRefPubMedWeb of Science
  16. ↵
    1. Del Rio D ,
    2. Stewart AJ ,
    3. Pellegrini N
    . A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005;15:316–28.doi:10.1016/j.numecd.2005.05.003 pmid:http://www.ncbi.nlm.nih.gov/pubmed/16054557
    OpenUrlCrossRefPubMedWeb of Science
  17. ↵
    1. Lashkarizadeh MR ,
    2. Garshasbi M ,
    3. Shabani M , et al
    . Impact of opium addiction on levels of pro- and anti-inflammatory cytokines after surgery. Addict Health 2016;8:9.pmid:http://www.ncbi.nlm.nih.gov/pubmed/27274788
    OpenUrlPubMed
  18. ↵
    1. Li H ,
    2. Horke S ,
    3. Förstermann U
    . Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis 2014;237:208–19.doi:10.1016/j.atherosclerosis.2014.09.001 pmid:http://www.ncbi.nlm.nih.gov/pubmed/25244505
    OpenUrlCrossRefPubMed
  19. ↵
    1. Liang K ,
    2. Dong S-R ,
    3. Peng H
    . Serum levels and clinical significance of IFN-γ and IL-10 in patients with coronary heart disease. Eur Rev Med Pharmacol Sci 2016;20:1339–43.pmid:http://www.ncbi.nlm.nih.gov/pubmed/27097956
    OpenUrlPubMed
  20. ↵
    1. Asadikaram G ,
    2. Ram M ,
    3. Izadi A , et al
    . The study of the serum level of IL-4, TGF-β, IFN-γ, and IL-6 in overweight patients with and without diabetes mellitus and hypertension. J Cell Biochem 2019;120:4147–57.doi:10.1002/jcb.27700 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30260038
    OpenUrlPubMed
  21. ↵
    1. Mohammadpour-Gharehbagh A ,
    2. Jahantigh D ,
    3. Eskandari M , et al
    . Genetic and epigenetic analysis of the Bax and Bcl2 in the placenta of pregnant women complicated by preeclampsia. Apoptosis 2019;24:301–11.doi:10.1007/s10495-018-1501-8 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30701356
    OpenUrlPubMed
  22. ↵
    1. Buege JA ,
    2. Aust SD
    . Microsomal lipid peroxidation. In: Methods in enzymology. Elsevier, 1978: 302–10.
  23. ↵
    1. Juybari KB ,
    2. Ebrahimi G ,
    3. Momeni Moghaddam MA , et al
    . Evaluation of serum arsenic and its effects on antioxidant alterations in relapsing-remitting multiple sclerosis patients. Mult Scler Relat Disord 2018;19:79–84.doi:10.1016/j.msard.2017.11.010 pmid:http://www.ncbi.nlm.nih.gov/pubmed/29156301
    OpenUrlPubMed
  24. ↵
    1. Tsikas D
    . Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: appraisal of the Griess reaction in the L-arginine/nitric oxide area of research. J Chromatogr B Analyt Technol Biomed Life Sci 2007;851:51–70.doi:10.1016/j.jchromb.2006.07.054 pmid:http://www.ncbi.nlm.nih.gov/pubmed/16950667
    OpenUrlCrossRefPubMed
  25. ↵
    1. Ghasemi A ,
    2. Zahediasl S ,
    3. Azizi F
    . Elevated nitric oxide metabolites are associated with obesity in women. Arch Iran Med 2013;16:521.doi:013169/AIM.008 pmid:http://www.ncbi.nlm.nih.gov/pubmed/23981155
    OpenUrlPubMed
  26. ↵
    1. Karimi A ,
    2. Bahrampour K ,
    3. Momeni Moghaddam MA , et al
    . Evaluation of lithium serum level in multiple sclerosis patients: a neuroprotective element. Mult Scler Relat Disord 2017;17:244–8.doi:10.1016/j.msard.2017.08.019 pmid:http://www.ncbi.nlm.nih.gov/pubmed/29055468
    OpenUrlPubMed
  27. ↵
    1. Azzawi M ,
    2. Hasleton P
    . Tumour necrosis factor alpha and the cardiovascular system: its role in cardiac allograft rejection and heart disease. Cardiovasc Res 1999;43:850–9.doi:10.1016/S0008-6363(99)00138-8 pmid:http://www.ncbi.nlm.nih.gov/pubmed/10615412
    OpenUrlCrossRefPubMed
  28. ↵
    1. Yarahmadzehi S ,
    2. Fanaei H ,
    3. Mirshekar MA , et al
    . Opium consumption exerts protective effect against cerebral ischemia through reducing inflammation and enhancing antioxidant defense in male rats. Neurol Psychiatry Brain Res 2020;37:15–20.doi:10.1016/j.npbr.2020.05.005
    OpenUrl
  29. ↵
    1. Zhao S-ping ,
    2. Wu Z-hong ,
    3. Wu J ,
    4. S-p Z ,
    5. Z-h W , et al
    . Effect of atorvastatin on tumor necrosis factor alpha serum concentration and mRNA expression of adipose in hypercholesterolemic rabbits. J Cardiovasc Pharmacol 2005;46:185–9.doi:10.1097/01.fjc.0000167017.69468.61 pmid:http://www.ncbi.nlm.nih.gov/pubmed/16044030
    OpenUrlCrossRefPubMed
  30. ↵
    1. McFarland AJ ,
    2. Davey AK ,
    3. Anoopkumar-Dukie S
    . Statins reduce lipopolysaccharide-induced cytokine and inflammatory mediator release in an in vitro model of microglial-like cells. Mediators Inflamm 2017;2017:1–10.doi:10.1155/2017/2582745 pmid:http://www.ncbi.nlm.nih.gov/pubmed/28546657
    OpenUrlCrossRefPubMed
  31. ↵
    1. Al-Bahrani A ,
    2. Taha S ,
    3. Shaath H , et al
    . TNF-α and IL-8 in acute stroke and the modulation of these cytokines by antiplatelet agents. Curr Neurovasc Res 2007;4:31–7.doi:10.2174/156720207779940716 pmid:http://www.ncbi.nlm.nih.gov/pubmed/17311542
    OpenUrlCrossRefPubMed
  32. ↵
    1. Skrabalova J ,
    2. Drastichova Z ,
    3. Novotny J
    . Morphine as a potential oxidative stress-causing agent. Mini Rev Org Chem 2013;10:367–72.doi:10.2174/1570193X113106660031 pmid:http://www.ncbi.nlm.nih.gov/pubmed/24376392
    OpenUrlPubMed
  33. ↵
    1. Sawaya BE ,
    2. Deshmane SL ,
    3. Mukerjee R , et al
    . TNF alpha production in morphine-treated human neural cells is NF-kappaB-dependent. J Neuroimmune Pharmacol 2009;4:140–9.doi:10.1007/s11481-008-9137-z pmid:http://www.ncbi.nlm.nih.gov/pubmed/19023660
    OpenUrlCrossRefPubMed
  34. ↵
    1. Peng X ,
    2. Mosser DM ,
    3. Adler MW , et al
    . Morphine enhances interleukin-12 and the production of other pro-inflammatory cytokines in mouse peritoneal macrophages. J Leukoc Biol 2000;68:723–8.pmid:http://www.ncbi.nlm.nih.gov/pubmed/11073113
    OpenUrlPubMedWeb of Science
  35. ↵
    1. Yamashita H ,
    2. Shimada K ,
    3. Seki E , et al
    . Concentrations of interleukins, interferon, and C-reactive protein in stable and unstable angina pectoris. Am J Cardiol 2003;91:133–6.doi:10.1016/S0002-9149(02)03097-7 pmid:http://www.ncbi.nlm.nih.gov/pubmed/12521622
    OpenUrlCrossRefPubMedWeb of Science
  36. ↵
    1. Clarke R ,
    2. Valdes-Marquez E ,
    3. Hill M , et al
    . Plasma cytokines and risk of coronary heart disease in the PROCARDIS study. Open Heart 2018;5:e000807.doi:10.1136/openhrt-2018-000807 pmid:http://www.ncbi.nlm.nih.gov/pubmed/29713486
    OpenUrlAbstract/FREE Full Text
  37. ↵
    1. McLaren JE ,
    2. Ramji DP
    . Interferon gamma: a master regulator of atherosclerosis. Cytokine Growth Factor Rev 2009;20:125–35.doi:10.1016/j.cytogfr.2008.11.003 pmid:http://www.ncbi.nlm.nih.gov/pubmed/19041276
    OpenUrlCrossRefPubMedWeb of Science
  38. ↵
    1. Enayati S ,
    2. Seifirad S ,
    3. Amiri P , et al
    . Interleukin-1 beta, interferon-gamma, and tumor necrosis factor-alpha gene expression in peripheral blood mononuclear cells of patients with coronary artery disease. ARYA Atheroscler 2015;11:267.pmid:http://www.ncbi.nlm.nih.gov/pubmed/26715931
    OpenUrlPubMed
  39. ↵
    1. Krzystolik A ,
    2. Dziedziejko V ,
    3. Safranow K , et al
    . Is plasma soluble CD36 associated with cardiovascular risk factors in early onset coronary artery disease patients? Scand J Clin Lab Invest 2015;75:398–406.doi:10.3109/00365513.2015.1031693 pmid:http://www.ncbi.nlm.nih.gov/pubmed/25916834
    OpenUrlPubMed
  40. ↵
    1. Paulsson JM ,
    2. Held C ,
    3. Jacobson SH , et al
    . In vivo extravasated human monocytes have an altered expression of CD16, HLA-DR, CD86, CD36 and CX(3)CR1. Scand J Immunol 2009;70:368–76.doi:10.1111/j.1365-3083.2009.02306.x pmid:http://www.ncbi.nlm.nih.gov/pubmed/19751271
    OpenUrlCrossRefPubMed
  41. ↵
    1. Chistiakov DA ,
    2. Killingsworth MC ,
    3. Myasoedova VA , et al
    . CD68/macrosialin: not just a histochemical marker. Lab Invest 2017;97:4–13.doi:10.1038/labinvest.2016.116 pmid:http://www.ncbi.nlm.nih.gov/pubmed/27869795
    OpenUrlCrossRefPubMed
  42. ↵
    1. Morris T ,
    2. Stables M ,
    3. Hobbs A , et al
    . Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol 2009;183:2089–96.doi:10.4049/jimmunol.0900477 pmid:http://www.ncbi.nlm.nih.gov/pubmed/19597002
    OpenUrlAbstract/FREE Full Text
  43. ↵
    1. Momeni-Moghaddam MA ,
    2. Asadikaram G ,
    3. Nematollahi MH , et al
    . Effects of cigarette smoke and opium on the expression of CD9, CD36, and CD68 at mRNA and protein levels in human macrophage cell line THP-1. Iran J Allergy Asthma Immunol 2020;19:45-55.doi:10.18502/ijaai.v19i1.2417 pmid:http://www.ncbi.nlm.nih.gov/pubmed/32245320
    OpenUrlPubMed
  44. ↵
    1. Huang W ,
    2. Febbraio M ,
    3. Silverstein RL
    . CD9 tetraspanin interacts with CD36 on the surface of macrophages: a possible regulatory influence on uptake of oxidized low density lipoprotein. PLoS One 2011;6:e29092.doi:10.1371/journal.pone.0029092 pmid:http://www.ncbi.nlm.nih.gov/pubmed/22216174
    OpenUrlCrossRefPubMed
  45. ↵
    1. Jin Y ,
    2. Tachibana I ,
    3. Takeda Y , et al
    . Statins decrease lung inflammation in mice by upregulating tetraspanin CD9 in macrophages. PLoS One 2013;8:e73706.doi:10.1371/journal.pone.0073706 pmid:http://www.ncbi.nlm.nih.gov/pubmed/24040034
    OpenUrlCrossRefPubMed
  46. ↵
    1. Lee R ,
    2. Margaritis M ,
    3. Channon KM , et al
    . Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations. Curr Med Chem 2012;19:2504–20.doi:10.2174/092986712800493057 pmid:http://www.ncbi.nlm.nih.gov/pubmed/22489713
    OpenUrlCrossRefPubMed
  47. ↵
    1. Mohammadi A ,
    2. Mirzaei F ,
    3. Jamshidi M , et al
    . The in vivo biochemical and oxidative changes by ethanol and opium consumption in Syrian hamsters. Int J Biol 2013;5:14.doi:10.5539/ijb.v5n4p14
    OpenUrl
  48. ↵
    1. Bhat MA ,
    2. Mahajan N ,
    3. Gandhi G
    . Oxidative stress status in coronary artery disease patients. Int J Life Sc Bt Pharm Res 2012;1:236–43.
    OpenUrl
  49. ↵
    1. Khaki-Khatibi F ,
    2. Samadi N ,
    3. Yaghoubi A
    . Association between inflammatory factor, lipid peroxidation and total-antioxidant in non-diabetic patients of coronary artery disease. J Clin Anal Med 2014;2.
  50. ↵
    1. Pacher P ,
    2. Beckman JS ,
    3. Liaudet L
    . Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007;87:315–424.doi:10.1152/physrev.00029.2006 pmid:http://www.ncbi.nlm.nih.gov/pubmed/17237348
    OpenUrlCrossRefPubMedWeb of Science
  51. ↵
    1. Shreshtha S ,
    2. Sharma P ,
    3. Kumar P
    . Nitric Oxide: It’s Role in Immunity. J Clin Diagnostic Res 2018;12.doi:10.7860/JCDR/2018/31817.11764
  52. ↵
    1. Ghazavi A ,
    2. Mosayebi G ,
    3. Solhi H , et al
    . Serum markers of inflammation and oxidative stress in chronic opium (Taryak) smokers. Immunol Lett 2013;153:22–6.doi:10.1016/j.imlet.2013.07.001 pmid:http://www.ncbi.nlm.nih.gov/pubmed/23850638
    OpenUrlCrossRefPubMed
  53. ↵
    1. Mahmoodi K ,
    2. Nasehi L ,
    3. Karami E , et al
    . Association of nitric oxide levels and endothelial nitric oxide synthase G894T polymorphism with coronary artery disease in the Iranian population. Vasc Specialist Int 2016;32:105–12.doi:10.5758/vsi.2016.32.3.105 pmid:http://www.ncbi.nlm.nih.gov/pubmed/27699157
    OpenUrlPubMed
  54. ↵
    1. Kalantarian G ,
    2. Rezaei M ,
    3. Homayonfar S , et al
    . Effect of walnut consumption on serum lipid profiles, high-sensitivity C-reactive protein and nitric oxide in patients with coronary artery disease. Jentashapir J Health Res 2015;6.doi:10.5812/jjhr.27196
  55. ↵
    1. Yoon Y ,
    2. Song J ,
    3. Hong SH , et al
    . Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease. Clin Chem 2000;46:1626–30.doi:10.1093/clinchem/46.10.1626 pmid:http://www.ncbi.nlm.nih.gov/pubmed/11017941
    OpenUrlAbstract/FREE Full Text
  56. ↵
    1. Adela R ,
    2. Nethi SK ,
    3. Bagul PK , et al
    . Hyperglycaemia enhances nitric oxide production in diabetes: a study from South Indian patients. PLoS One 2015;10:e0125270.doi:10.1371/journal.pone.0125270 pmid:http://www.ncbi.nlm.nih.gov/pubmed/25894234
    OpenUrlPubMed
  57. ↵
    1. Sadeghian S ,
    2. Darvish S ,
    3. Davoodi G , et al
    . The association of opium with coronary artery disease. Eur J Cardiovasc Prev Rehabil 2007;14:715–7.doi:10.1097/HJR.0b013e328045c4e9 pmid:http://www.ncbi.nlm.nih.gov/pubmed/17925633
    OpenUrlPubMedWeb of Science
  58. ↵
    1. Dehghani F ,
    2. Masoomi M ,
    3. Haghdoost AA
    . Relation of opium addiction with the severity and extension of myocardial infarction and its related mortality. Addict Health 2013;5:35.pmid:http://www.ncbi.nlm.nih.gov/pubmed/24494156
    OpenUrlPubMed
  59. ↵
    1. Sharafi A ,
    2. Pour Hosseini HR ,
    3. Jalali A , et al
    . Opium consumption and mid-term outcome of percutaneous coronary intervention in men. J Tehran Heart Cent 2014;9:115.pmid:http://www.ncbi.nlm.nih.gov/pubmed/25870628
    OpenUrlPubMed
  60. ↵
    1. Roohafza H ,
    2. Talaei M ,
    3. Sadeghi M , et al
    . Opium decreases the age at myocardial infarction and sudden cardiac death: a long- and short-term outcome evaluation. Arch Iran Med 2013;16:154-60.doi:013163/AIM.007 pmid:http://www.ncbi.nlm.nih.gov/pubmed/23432167
    OpenUrlPubMed
PreviousNext
Back to top
Vol 70 Issue 8 Table of Contents
Journal of Investigative Medicine: 70 (8)
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Front Matter (PDF)
Email

Thank you for your interest in spreading the word on JIM.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68
(Your Name) has sent you a message from JIM
(Your Name) thought you would like to see the JIM web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Alerts
Sign In to Email Alerts with your Email Address
Citation Tools
Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68
Mohammad Amin Momeni-Moghaddam, Gholamreza Asadikaram, Mohammad Masoumi, Erfan Sadeghi, Hamed Akbari, Moslem Abolhassani, Alireza Farsinejad, Morteza Khaleghi, Mohammad Hadi Nematollahi, Shahriar Dabiri, Mohammad Kazemi Arababadi
Journal of Investigative Medicine Dec 2022, 70 (8) 1728-1735; DOI: 10.1136/jim-2021-001935

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Cite This
  • APA
  • Chicago
  • Endnote
  • MLA
Loading
Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68
Mohammad Amin Momeni-Moghaddam, Gholamreza Asadikaram, Mohammad Masoumi, Erfan Sadeghi, Hamed Akbari, Moslem Abolhassani, Alireza Farsinejad, Morteza Khaleghi, Mohammad Hadi Nematollahi, Shahriar Dabiri, Mohammad Kazemi Arababadi
Journal of Investigative Medicine Dec 2022, 70 (8) 1728-1735; DOI: 10.1136/jim-2021-001935
Download PDF

Share
Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68
Mohammad Amin Momeni-Moghaddam, Gholamreza Asadikaram, Mohammad Masoumi, Erfan Sadeghi, Hamed Akbari, Moslem Abolhassani, Alireza Farsinejad, Morteza Khaleghi, Mohammad Hadi Nematollahi, Shahriar Dabiri, Mohammad Kazemi Arababadi
Journal of Investigative Medicine Dec 2022, 70 (8) 1728-1735; DOI: 10.1136/jim-2021-001935
Reddit logo Twitter logo Facebook logo Mendeley logo
Respond to this article
  • Tweet Widget
  • Facebook Like
  • Google Plus One
  • Article
    • Abstract
    • Introduction
    • Materials and methods
    • Results
    • Discussion
    • Conclusions
    • Data availability statement
    • Ethics statements
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • eLetters
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Altered degree centrality in patients with non-neuropsychiatric systemic lupus erythematosus: a resting-state fMRI study
  • Organochlorine pesticides, oxidative stress biomarkers, and leukemia: a case-control study
  • Temporal trends and disparities in gastroenterology care use before, during, and after COVID-19 lockdown
Show more Original research

Similar Articles

 

CONTENT

  • Latest content
  • Current issue
  • Archive
  • Sign up for email alerts
  • RSS

JOURNAL

  • About the journal
  • Editorial board
  • Subscribe
  • Thank you to our reviewers
  • American Federation for Medical Research

AUTHORS

  • Information for authors
  • Submit a paper
  • Track your article
  • Open Access at BMJ

HELP

  • Contact us
  • Reprints
  • Permissions
  • Advertising
  • Feedback form

© 2023 American Federation for Medical Research