REVIEW PAPER<br>Therapeutic potential of heme oxygenase-1in cardiovascular disease

Heme oxygenase-1 (HO1) degrades heme to carbon monoxide (CO), biliverdin, and ferrous iron. Through these<br /> products, HO1 mitigates cellular injury by exerting anti-oxidant, anti-apoptotic, and anti-inflammatory effects.<br /> Several lines of evidence indicate that angiogenic factors, such as vascular endothelial growth factor A (VEGF)<br /> and stromal cell-derived factor 1 (SDF1), mediate their proangiogenic action in endothelial cells and endothelial<br /> progenitor cells through induction of HO1, and reciprocally, VEGF and SDF1 are enhanced by HO1 overexpression.<br /> Ferrous iron released during the breakdown of free heme by HO1 is an extremely pro-oxidative molecule<br /> that can be rapidly removed by ferritin. Of note, this iron sequestering protein also has been shown to exert some<br /> proangiogenic effects. Moreover, our recent data indicate that HO1 is an important mediator of differentiation<br /> and function of stem cells, including endothelial and myoblasts progenitors. All of this makes HO1 a promising<br /> target for novel cardiovascular therapies. The aim of this review is to discuss the existing knowledge and to propose<br /> the therapeutic approaches, which have to consider the necessity of tight regulation of HO1 expression.