Drug Discovery Center and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Pathophysiology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
Biochem Pharmacol. 2022 Jan;195:114866. doi: 10.1016/j.bcp.2021.114866. Epub 2021 Dec 2.
Cardiovascular and heart diseases are leading causes of morbidity and mortality. Coronary artery endothelial and vascular dysfunction, inflammation, and mitochondrial dysfunction contribute to progression of heart diseases such as arrhythmias, congestive heart failure, and heart attacks. Classes of fatty acid epoxylipids and their enzymatic regulation by soluble epoxide hydrolase (sEH) have been implicated in coronary artery dysfunction, inflammation, and mitochondrial dysfunction in heart diseases. Likewise, genetic and pharmacological manipulations of epoxylipids have been demonstrated to have therapeutic benefits for heart diseases. Increasing epoxylipids reduce cardiac hypertrophy and fibrosis and improve cardiac function. Beneficial actions for epoxylipids have been demonstrated in cardiac ischemia reperfusion injury, electrical conductance abnormalities and arrhythmias, and ventricular tachycardia. This review discusses past and recent findings on the contribution of epoxylipids in heart diseases and the potential for their manipulation to treat heart attacks, arrhythmias, ventricular tachycardia, and heart failure.
心血管疾病和心脏病是发病率和死亡率的主要原因。冠状动脉内皮和血管功能障碍、炎症和线粒体功能障碍导致心律失常、充血性心力衰竭和心脏病发作等疾病的进展。脂肪酸环氧化物及其可溶性环氧化物水解酶 (sEH) 的酶调节类已被牵连到冠状动脉功能障碍、炎症和线粒体功能障碍在心脏病。同样，环氧化物的遗传和药物操纵已被证明对心脏病有治疗益处。增加环氧化物可减少心肌肥大和纤维化，改善心脏功能。在心肌缺血再灌注损伤、电导率异常和心律失常以及室性心动过速中已经证明了环氧化物的有益作用。这篇综述讨论了过去和最近关于环氧化物在心脏病中的作用的发现，以及对其进行操纵以治疗心脏病发作、心律失常、室性心动过速和心力衰竭的潜力。
