RT Journal Article
SR Electronic
T1 Differential gene expression in patients with primary mitral valve disease: identifying potential therapeutic targets in the era of precision medicine
JF Journal of Investigative Medicine
JO J Investig Med
FD BMJ Publishing Group Ltd
SP 1289
OP 1291
DO 10.1136/jim-2020-001467
VO 68
IS 7
A1 Emily Shih
A1 John J Squiers
A1 Jacob Turner
A1 Michael DiMaio
A1 William T Brinkman
A1 Robert L Smith
YR 2020
UL http://hw-f5-jim.highwire.org/content/68/7/1289.abstract
AB Primary (degenerative) mitral valve (MV) disease is a result of structural remodeling due to degenerative and adaptive changes of MV tissue. We hypothesized that in patients with primary MV disease undergoing surgery for severe mitral regurgitation (MR), a distinct genetic expression profile within the MV leaflet tissue could be identified as compared with patients without MV disease. Tissue samples from the MV leaflets of 65 patients undergoing MV surgery for MR due to primary MV disease and 4 control cadavers without MV disease were collected and analyzed. MicroRNA transcripts were hybridized to Illumina HumanHT-12 v4 Beadchips. Ingenuity pathway analyses (IPAs) were conducted to provide biological interpretation. Of the approximately 20 000 genes examined, 4092 (20%) were differentially expressed between patients with primary MV disease and normal controls (false discovery rate<0.05). The differentially expressed genes could be clustered into five regulator effect networks from the Ingenuity Knowledge IPA database with a consistency score of >6. These five networks have been previously implicated in pathophysiological cardiac abnormalities, including inhibited contractility of the heart and fatty acid oxidation as well as activation of apoptosis of smooth muscle cells, cardiac degeneration, and hypertrophy of cardiac cells. MV tissue in patients with primary MV disease demonstrated distinct genetic expression patterns as compared with normal controls. Further studies are necessary to determine whether the molecular pathways identified in this experiment may represent potential therapeutic targets to prevent degeneration of MV tissue leading to severe MR.