Protective role of heme oxygenase-1 against inflammation in atherosclerosis

Front Biosci (Landmark Ed). 2011 Jun 1;16:2372-88. doi: 10.2741/3860.

Abstract

Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting step in the metabolism of free heme into equimolar amounts of ferrous iron, carbon monoxide (CO), and biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. HO-1 has recently been identified as a promising therapeutic target in the treatment of vascular inflammatory disease, including atherosclerosis. HO-1 represses inflammation by removing the pro-inflammatory molecule heme and by generating CO and the bile pigments, biliverdin and bilirubin. These HO-1 reaction products are capable of blocking innate and adaptive immune responses by modifying the activation, differentiation, maturation, and/or polarization of numerous immune cells, including endothelial cells, monocytes/macrophages, dendritic cells, T lymphocytes, mast cells, and platelets. These cellular actions by CO and bile pigments result in diminished leukocyte recruitment and infiltration, and pro-inflammatory mediator production within atherosclerotic lesions. This review highlights the mechanisms by which HO-1 suppresses vascular inflammation in atherosclerosis, and explores possible therapeutic modalities by which HO-1 and its reaction products can be employed to ameliorate vascular inflammatory disease.

Publication types

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

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy
  • Atherosclerosis / enzymology*
  • Atherosclerosis / immunology
  • Cytokines / metabolism
  • Heme / metabolism
  • Heme Oxygenase-1 / deficiency
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / enzymology*
  • Inflammation / immunology
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism
  • Mice
  • Mice, Knockout
  • Models, Biological

Substances

  • Cytokines
  • Inflammation Mediators
  • Heme
  • Heme Oxygenase-1