PT  - JOURNAL ARTICLE
AU  - Hong-Hong Li
AU  - Li-Jian Xie
AU  - Ting-Ting Xiao
AU  - Min Huang
AU  - Jie Shen
TI  - Mibefradil suppresses the proliferation of pulmonary artery smooth muscle cells
AID  - 10.1136/jim-d-15-00167
DP  - 2016 Jan 01
TA  - Journal of Investigative Medicine
PG  - 45--49
VI  - 64
IP  - 1
4099  - http://hw-f5-jim.highwire.org/content/64/1/45.short
4100  - http://hw-f5-jim.highwire.org/content/64/1/45.full
SO  - J Investig Med2016 Jan 01; 64
AB  - Intracellular Ca2+ levels play a critical role in the regulation of vasodilation and vasoconstriction by stimulating pulmonary artery smooth muscle cell (PASMC) proliferation, which is important in the pathogenesis of pulmonary arterial hypertension (PAH); however, L-type Ca2+ channel antagonists are useful in only few patients with PAH. The present study sought to assess the effect of mibefradil, which blocks T-type Ca2+ channels, on PASMC proliferation and Ca2+ channel profile. Human PASMCs were stimulated with 25 ng/mL platelet-derived growth factor-BB (PDGF-BB) with and without 10 µM mibefradil or 100 nM sildenafil. After 48 or 72 h, PASMC proliferation and Ca2+ channel expression were assessed by MTT assays and western blot analysis, respectively. PDGF-BB-induced PASMC proliferation at 72 h (p<0.01), which was inhibited by both sildenafil and mibefradil (p<0.01). Transient receptor potential Ca2+ channel 6 (TRPC6) expression was significantly increased with PDGF-BB stimulation (p=0.009); however, no changes in TRPC1, TRPC3, CAV1.2, and CAV3.2 levels were observed. Although both TRPC1 and CAV1.2 expression levels were increased in PDGF-stimulated PASMCs on mibefradil and sildenafil treatment, it was not statistically significant (p=0.086 and 1.000, respectively). Mibefradil inhibits PDGF-BB-stimulated PASMC proliferation; however, the mechanism through which it functions remains to be determined. Further studies are required to elucidate the full therapeutic value of mibefradil for PAH.