Eicosanoids via CYP450 and cardiovascular disease: Hints from genetic and nutrition studies

Prostaglandins Other Lipid Mediat. 2018 Nov:139:41-47. doi: 10.1016/j.prostaglandins.2018.10.001. Epub 2018 Oct 5.

Abstract

Metabolites of arachidonic acid via CYP450 such as epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE), have vasoactive and natriuretic properties and have been implicated in BP homeostasis and the incidence of cardio- and cerebrovascular diseases in animal studies. In humans, genetic studies considering genes implicated in arachidonic acids metabolism (CYP4F2, CYP4A11, CYP2J2, CYP2C8, CYP2C9, CYP2A1/2, EPHX2) can offer a hint to understand their role, if any, in hypertension development and its deleterious cardiovascular effects. Candidate genes studies and successive meta-analyses have shown that specific single nucleotide polymorphisms (SNPs), often functional, and haplotypes in these genes were associated with one or more cardiovascular endpoints. Nevertheless, genome wide association studies (GWAS) have never detected any SNPs nearby these genes (the only exception being the CYP2A1/2 locus) as associated with either BP, hypertension, coronary artery disease or stroke questioning their real importance for cardiovascular health in humans. Nutrition studies exploring the effects of specific foods on the formation of these compounds or others through the same pathway can offer new insights on this field.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cytochrome P-450 Enzyme System / genetics*
  • Eicosanoids / genetics*
  • Eicosanoids / metabolism
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Haplotypes / genetics
  • Humans
  • Hydroxyeicosatetraenoic Acids / genetics
  • Nutrition Disorders / genetics
  • Nutrition Disorders / metabolism
  • Nutrition Disorders / pathology
  • Polymorphism, Single Nucleotide / genetics

Substances

  • Eicosanoids
  • Hydroxyeicosatetraenoic Acids
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid
  • Cytochrome P-450 Enzyme System