20-HETE in the regulation of vascular and cardiac function

Pharmacol Ther. 2018 Dec:192:74-87. doi: 10.1016/j.pharmthera.2018.07.004. Epub 2018 Jul 23.

Abstract

20-HETE, the ω-hydroxylation product of arachidonic acid catalyzed by enzymes of the cytochrome P450 (CYP) 4A and 4F gene families, is a bioactive lipid mediator with potent effects on the vasculature including stimulation of smooth muscle cell contractility, migration and proliferation as well as activation of endothelial cell dysfunction and inflammation. Clinical studies have shown elevated levels of plasma and urinary 20-HETE in human diseases and conditions such as hypertension, obesity and metabolic syndrome, myocardial infarction, stroke, and chronic kidney diseases. Studies of polymorphic associations also suggest an important role for 20-HETE in hypertension, stroke and myocardial infarction. Animal models of increased 20-HETE production are hypertensive and are more susceptible to cardiovascular injury. The current review summarizes recent findings that focus on the role of 20-HETE in the regulation of vascular and cardiac function and its contribution to the pathology of vascular and cardiac diseases.

Keywords: 20-HETE; Angiogenesis; Cytochrome P450; Heart failure; Hypertension; Myocardial infarction; Vascular remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / physiopathology
  • Endothelium, Vascular / metabolism*
  • ErbB Receptors / metabolism
  • Humans
  • Hydroxyeicosatetraenoic Acids / biosynthesis*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Physiologic / physiology
  • Obesity / metabolism
  • Obesity / physiopathology
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • Vascular Remodeling*

Substances

  • Hydroxyeicosatetraenoic Acids
  • Receptors, G-Protein-Coupled
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid
  • ErbB Receptors