Role of heme oxygenase-1 in the regulation of blood pressure and cardiac function.
Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of the properties of inducible HO (HO-1) and its products, we hypothesized that HO-1 would play an important role in the regulation of cardiovascular function. In this article, we will review the role of HO-1 in the regulation of blood pressure and cardiac function and highlight previous studies from our laboratory using gene deletion and gene overexpression transgenic approaches in mice. These studies will include the investigation of HO-1 in the setting of hypertension (renovascular), hypotension (endotoxemia), and ischemia/reperfusion injury (heart). In a chronic renovascular hypertension model, hypertension, cardiac hypertrophy, acute renal failure, and acute mortality induced by one kidney-one clip surgery were more severe in HO-1-null mice. In addition, HO-1-null mice with endotoxemia had earlier resolution of hypotension, yet the mortality and the incidence of end-organ damage were higher in the absence of HO-1. In contrast, mice with cardiac-specific overexpression of HO-1 had an improvement in cardiac function, smaller myocardial infarctions, and reduced inflammatory and oxidative damage after coronary artery ligation and reperfusion. Taken together, these studies suggest that an absence of HO-1 has detrimental consequences, whereas overexpression of HO-1 plays a protective role in hypoperfusion and ischemia/reperfusion injury.
Chen
Yen-Hsu
YH
Pulmonary and Critical Care Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Yet
Shaw-Fang
SF
Perrella
Mark A
MA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D019446:Endotoxemia / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007668:Kidney / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism
D008070:Lipopolysaccharides; D008565:Membrane Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse