Heme oxygenase-1 and the Vascular Bed: From Molecular Mechanisms to Therapeutic Opportunities

Antioxid Redox Signal. 2008 Oct;10(10):1767-812. doi: 10.1089/ars.2008.2043.

Abstract

Heme oxygenase-1, an enzyme degrading heme to carbon monoxide, iron, and biliverdin, has been recognized as playing a crucial role in cellular defense against stressful conditions, not only related to heme release. HO-1 protects endothelial cells from apoptosis, is involved in blood-vessel relaxation regulating vascular tone, attenuates inflammatory response in the vessel wall, and participates in blood-vessel formation by means of angiogenesis and vasculogenesis. The latter functions link HO-1 not only to cardiovascular ischemia but also to many other conditions that, like development, wound healing, or cancer, are dependent on neovascularization. The aim of this comprehensive review is to address the mechanisms of HO-1 regulation and function in cardiovascular physiology and pathology and to demonstrate some possible applications of the vast knowledge generated so far. Recent data provide powerful evidence for the involvement of HO-1 in the therapeutic effect of drugs used in cardiovascular diseases. Novel studies open the possibilities of application of HO-1 for gene and cell therapy. Therefore, research in forthcoming years should help to elucidate both the real role of HO-1 in the effect of drugs and the clinical feasibility of HO-1-based cell and gene therapy, creating the effective therapeutic avenues for this refined antioxidant system.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Biliverdine / metabolism
  • Carbon Monoxide / metabolism
  • Carbon Monoxide / pharmacology
  • Carbon Monoxide / toxicity
  • Cardiovascular Agents / pharmacology
  • Cardiovascular Agents / therapeutic use
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / enzymology
  • Cardiovascular Diseases / therapy
  • Child
  • Diabetes Complications / enzymology
  • Diabetes Complications / prevention & control
  • Diabetes Complications / therapy
  • Endothelium, Vascular / enzymology*
  • Enzyme Induction / drug effects
  • Enzyme Induction / radiation effects
  • Female
  • Genetic Therapy
  • Heme / metabolism
  • Heme Oxygenase-1 / chemistry
  • Heme Oxygenase-1 / deficiency
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / physiology*
  • Humans
  • Inflammation / enzymology
  • Inflammation / therapy
  • Iron / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Neovascularization, Physiologic
  • Rabbits
  • Rats
  • Vasomotor System / drug effects

Substances

  • Cardiovascular Agents
  • Heme
  • Carbon Monoxide
  • Iron
  • Heme Oxygenase-1
  • Biliverdine