Mechanisms of isolevuglandin-protein adduct formation in inflammation and hypertension

Prostaglandins Other Lipid Mediat. 2018 Nov;139:48-53. doi: 10.1016/j.prostaglandins.2018.09.008. Epub 2018 Sep 29.

Abstract

Inflammation has been implicated in the pathogenesis of hypertension and recent evidence suggests that isolevuglandin (IsoLG)-protein adducts play a role. Several hypertensive stimuli contribute to formation of IsoLG-protein adducts including excess dietary salt and catecholamines. The precise intracellular mechanisms by which these hypertensive stimuli lead to IsoLG-protein adduct formation are still not well understood; however, there is now evidence implicating NADPH-oxidase derived reactive oxygen species (ROS) in this process. ROS oxidize arachidonic acid leading to formation of IsoLGs, which non-covalently adduct to lysine residues and alter protein structure and function. Recent studies suggest that these altered proteins act as neo-antigens leading to an autoimmune state that results in hypertension. The goal of this mini-review is to highlight some of the hypertensive stimuli and the mechanisms contributing to IsoLG-protein adduct formation leading to inflammation and hypertension.

Keywords: Hypertension; Inflammation; Isolevuglandins.

Publication types

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

MeSH terms

  • Humans
  • Hypertension / complications
  • Hypertension / genetics
  • Hypertension / metabolism*
  • Hypertension / pathology
  • Inflammation / complications
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Lipids / chemistry*
  • Lipids / genetics
  • Oxidation-Reduction
  • Oxidative Stress / genetics
  • Proteins / chemistry*
  • Proteins / genetics
  • Reactive Oxygen Species / metabolism

Substances

  • Lipids
  • Proteins
  • Reactive Oxygen Species
  • isolevuglandin