Heme oxygenase and atherosclerosis

Overproduction of reactive oxygen species under pathophysiological conditions, including dyslipidemia, hypertension, diabetes, and smoking, is integral in the development of cardiovascular diseases (CVD). The reactive oxygen species released from all types of vascular cells regulate various signaling pathways that mediate not only vascular inflammation in atherogenesis but also antioxidative and antiinflammatory responses. One such protective and stress-induced protein is heme oxygenase (HO). HO is the first rate-limiting enzyme in heme breakdown to generate equimolar quantities of carbon monoxide, biliverdin, and free ferrous iron. Accumulating evidence has shown that inducible HO (HO-1) and its products function as adaptive molecules against oxidative insults. The proposed mechanisms by which HO-1 exerts its cytoprotective effects include its abilities to degrade the pro-oxidative heme, to release biliverdin and subsequently convert it bilirubin, both of which have antioxidant properties, and to generate carbon monoxide, which has antiproliferative and antiinflammatory as well as vasodilatory properties. Herein, I highlight the relationship of HO and cardiovascular disease, especially atherosclerosis, gene-targeting approaches in animal models, and the potential for and concern about HO-1 as a novel therapeutic target for cardiovascular diseases.