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). Due to 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 cardiovascular function, and highlight our previous studies 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), atherosclerosis and vascular injury (vein graft stenosis), hypotension (endotoxemia), and ischemia / reperfusion injury (heart). In a chronic renovascular hypertension model, blood pressure elevation, cardiac hypertrophy, acute renal failure, and acute mortality induced by one kidney-one clip surgery are more severe in HO-1 null mice. Moreover, absence of HO-1 leads to accelerated atherosclerotic lesion formation and vein graft disease. In addition, HO-1 null mice with endotoxemia have earlier resolution of hypotension, yet the mortality and the incidence of end organ damage are higher in the absence of HO-1. In contrast, mice with cardiac-specific overexpression of HO-1 have an improvement in cardiac function, smaller myocardial infarcts, 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, while overexpression of HO-1 plays a protective role in ischemia / reperfusion injury.
Keywords: cytoprotection, hypertension, renovascular, atherosclerosis, vein graft stenosis, hypotension, endotoxemia, ischemia/reperfusion
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