Effects Of1-Oleoyl-2-Acetyl-Sn-glycerol On Expression Of Transient Receptor Potential Canonical (TRPC)3Channel And Calcineurin In Rat Hypertrophic Cardiomyocytes Induced By Pressure Overload

Objective: In the process of clinical treatment of hypertension, it issignificant not only to reduce high blood pressure, but also to prevent andtreat target organ damage. Myocardial hypertrophy and heart failure are themost common target organ damage. However, the pathogenesis ofhypertension and myocardial hypertrophy have not been clearly confirmed.Transient receptor potential channel (TRPC) as a nonselective cationchannel widely exists in cell membrane of human tissues, which isregulated by various factors, participates in the pathophysiological processof cardiovascular disease. In recent years, many studies have shown thatTRPC plays an important role in the process of myocardial hypertrophy inhypertension patients. It has been confirmed that TRPC3may effect theexpression of downstream signaling pathway to involve in the progress ofmyocardial hypertrophy in vitro, but little research study the effect ofmyocardial hypertrophy induced by high blood pressure using agonist or blocker to interfere TRPC channel in vivo. We aim to investigate the effectof TRPC3agonist1-oleoyl-2-acetyl-sn-glycerol(OAG) on expression oftransient receptor potential canonical3(TRPC3) channel and calcineurinAβ (CaN Aβ) in hypertrophic cardiomyocytes induced by pressureoverload.Methods: Left ventricular hypertrophy models were induced byabdominal aorta constriction (AAC). After1week,12male Sprague-Dawley model rats and12sham operation(SO) rats were randomly dividedinto SO group, SO+OAG group, abdominal aorta constriction (AAC)group,and AAC+OAG group, n=6in each group. After4weeks of OAGadministrated, blood pressure, left ventricular mass index(LVMI) and leftventricular transdiameter (LVTDM) of cardiomyocytes were measured.RT-PCR, immunohistochemistry and Western blot were used to detect thelevel of TRPC3and CaN Aβ mRNA and protein expression.Results: Compared with SO group, blood pressure, LVMI andLVTDM were significantly higher in AAC group[（170.7±9.3） vs（114.7±8.4）mm Hg,（2.77±0.11）vs（1.94±0.05）mg/g,（17.96±0.98）vs （14.08±0.85） μm, P＜0.05], which in AAC+OAG group weredramatically higher(P＜0.05) compared with AAC or SO+OAG group.Expression of TRPC3, CaN Aβ mRNA and protein level were existed ineach group, which in AAC group were higher compared with SO group,and which increased significantly in AAC+OAG group (P＜0.05) compared with AAC or SO+OAG group.The expression of TRPC3or CaNAβ between SO group and SO+OAG group had no significant difference.Conclusion: TRPC3and CaN Aβ may participate in the processes ofleft ventricular hypertrophy. OAG may promote TRPC3expression in thepathphysiological progresse of myocardial hypertrophy induced bypressure overload through activated calcium-dependent CaN Aβ in rats.Intervention of TRPC3may be a new pharmacological target to reversemyocardial hypertrophy induced by hypertension.