Abusive chronic alcohol consumption can cause metabolic and functional derangements in the heart and is a risk factor for development of non-ischemic cardiomyopathy. microRNA 214 (miR-214) is a molecular sensor of stress signals that negatively impacts cell survival. Considering cardioprotective and microRNA modulatory effects of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, we investigated the impact of chronic alcohol consumption on cardiac expression of miR-214 and its anti-apoptotic protein target, Bcl-2 and whether sildenafil attenuates such changes. Adult male FVB mice received unlimited access to either normal liquid diet (control), alcohol diet (35% daily calories intake), or alcohol + sildenafil (1 mg/kg/day, p.o.) for 14 weeks (n = 6–7/group). The alcohol-fed groups with or without sildenafil had increased total diet consumption and lower body weight as compared with controls. Echocardiography-assessed left ventricular function was unaltered by 14-week alcohol intake. Alcohol-fed group had 2.6-fold increase in miR-214 and significant decrease in Bcl-2 expression, along with enhanced phosphorylation of ERK1/2 and cleavage of PARP (marker of apoptotic DNA damage) in the heart. Co-ingestion with sildenafil blunted the alcohol-induced increase in miR-214, ERK1/2 phosphorylation, and maintained Bcl-2 and decreased PARP cleavage levels. In conclusion, chronic alcohol consumption triggers miR-214-mediated pro-apoptotic signaling in the heart, which was prevented by co-treatment with sildenafil. Thus, PDE5 inhibition may serve as a novel protective strategy against cardiac apoptosis due to chronic alcohol abuse.

长期滥用酒精会导致心脏代谢和功能紊乱，并且是发展为非缺血性心肌病的危险因素。microRNA 214 (miR-214) 是压力信号的分子传感器，会对细胞存活产生负面影响。考虑到磷酸二酯酶 5 (PDE5) 抑制剂西地那非的心脏保护和 microRNA 调节作用，我们研究了长期饮酒对 miR-214 及其抗凋亡蛋白靶标 Bcl-2 心脏表达的影响，以及西地那非是否会减弱这种变化。成年雄性 FVB 小鼠在 14 周内无限制地获得正常流质饮食（对照）、酒精饮食（每天摄入 35% 卡路里）或酒精 + 西地那非（1 mg/kg/天，口服）（n = 6–7/组）。与对照组相比，有或没有西地那非的酒精喂养组增加了总饮食消耗和降低了体重。超声心动图评估的左心室功能未因饮酒 14 周而改变。酒精喂养组的 miR-214 增加了 2.6 倍，Bcl-2 表达显着降低，同时心脏中 ERK1/2 的磷酸化和 PARP（凋亡 DNA 损伤的标志物）的切割增强。与西地那非共同摄入会减弱酒精诱导的 miR-214、ERK1/2 磷酸化增加，并维持 Bcl-2 并降低 PARP 切割水平。总之，长期饮酒会触发心脏中 miR-214 介导的促凋亡信号传导，而与西地那非联合治疗可以防止这种信号传导。因此，