Epoxylipids and soluble epoxide hydrolase in heart diseases

Biochem Pharmacol. 2022 Jan:195:114866. doi: 10.1016/j.bcp.2021.114866. Epub 2021 Dec 2.

Abstract

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.

Keywords: Coronary artery; Cytochrome P450; Eicosanoids; Heart failure; Hypertension; Inflammation; Mitochondrial function; Myocardial infarction; Soluble epoxide hydrolase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / enzymology
  • Arrhythmias, Cardiac / metabolism
  • Enzyme Inhibitors / therapeutic use
  • Epoxide Hydrolases / antagonists & inhibitors
  • Epoxide Hydrolases / metabolism*
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / metabolism*
  • Fatty Acids / metabolism*
  • Heart Diseases / drug therapy
  • Heart Diseases / enzymology
  • Heart Diseases / metabolism*
  • Heart Failure / drug therapy
  • Heart Failure / enzymology
  • Heart Failure / metabolism
  • Humans
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / metabolism
  • Solubility
  • Tachycardia, Ventricular / drug therapy
  • Tachycardia, Ventricular / enzymology
  • Tachycardia, Ventricular / metabolism

Substances

  • Enzyme Inhibitors
  • Epoxy Compounds
  • Fatty Acids
  • Epoxide Hydrolases