Protective role of heme oxygenase in the blood vessel wall during atherogenesis

Abstract

Several lines of evidence suggest that antioxidant processes and (or) endogenous antioxidants inhibit proatherogenic events in the blood vessel wall. Heme oxygenase (HO), which catabolizes heme to biliverdin, carbon monoxide, and catalytic iron, has been shown to have such antioxidative properties. The HO-1 isoform of heme oxygenase is ubiquitous and can be increased several fold by stimuli that induce cellular oxidative stress. Products of the HO reaction have important effects: carbon monoxide is a potent vasodilator, which is thought to play a role in modulation of vascular tone; biliverdin and its by-product bilirubin are potent antioxidants. Although HO induction results in an increase in catalytic free iron release, the enhancement of intracellular ferritin protein through HO-1 has been reported to decrease the cytotoxic effects of iron. Oxidized LDL has been shown to increase HO-1 expression in endothelial and smooth muscle cell cultures, and during atherogenesis. Further evidence of HO-1 expression associated with atherogenesis has been demonstrated in human, murine and rabbit atherosclerotic lesions. Moreover, genetic models of HO deficiency suggest that the actions of HO-1 are important in modulating the severity of atherosclerosis. Recent experiments in gene therapy using the HO gene suggest that interventions aimed at HO in the vessel wall could provide a novel therapeutic approach for the treatment or prevention of atherosclerotic disease.

Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells

“…The gene with the greatest level of increase in response to oxLDL was heme oxygenase 1 (HMOX1) ( Table 4). Several lines of evidence suggest that HMOX1 expression can be increased several fold by stimuli that induce cellular oxidative stress, including oxidized LDL (29,30). HMOX1 induction is known to lead to an increase in catalytic free iron release.…”

HO-1 Induced by Cilostazol Protects Against TNF-α-associated Cytotoxicity via a PPAR-γ-dependent Pathway in Human Endothelial Cells

“…Induction of HO-1 by either genetic approaches or pharmacological intervention has been shown to be effective in preventing or treating pulmonary hypertension in animal models [18,19]. Indeed, several studies support the notion [19] that HO-1 exerts an essential protective role in the vessel wall during atherogenesis [20,21]. However, the mechanism underlying the protection of endothelial cells by HO-1 from TNF-α-induced cytotoxicity remains to be clarified.…”

New Noninvasive Modalities in Coronary Angiography - Diagnostic Values of New Biomarkers for Cardiovascular Disease

“…On the other hand, it has been postulated that mild to moderate elevations of homocysteine in the general population predispose to atherosclerosis in a manner akin to the classic risk factors (Hackam & Anand, 2003). Additionally, the adaptive and protective responses of arterial vasculature against oxidative stress are important in the prevention of atherosclerosis (Hoekstra et al, 2004).…”

“…The heme oxygenase responsible for the degradation of heme grouping of hemoglobin is a stress inducible enzyme with antioxidative properties . The products of its reaction (bilirubine, carbon monoxide and iron) develop a potential protective role against atherosclerosis (Hoekstra et al, 2004). Studies have suggested that different circulating forms of bilirubin have the capacity to remove a variety of reactive species of oxygen, and inhibit the oxidation of LDL particles and the chemotaxis of monocytes, all of which are crucial steps in atherogenesis (Ghem et al, 2010).…”