Heme oxygenase-1 in cardiovascular diseases: molecular mechanisms and clinical perspectives.
Heme oxygenase (HO) catalyzes the rate-limiting step in the oxidative degradation of cellular heme that liberates iron, carbon monoxide (CO), and biliverdin. Two distinct HO isoforms have been identified in mammalian system. Compared to HO-2, which is constitutively expressed, HO-1 is a stressresponsive protein that is highly induced by many agents, including cytokines, endotoxin, heavy metals, nitric oxide and its own substrate heme. In addition to its well-defined role in heme catabolism and erythrocyte turnover, HO-1 also plays an important function in various physiological and pathophysiological states associated with cellular stress. Over the past decade, compelling evidence has revealed that the induction of HO-1 represents an important defensive mechanism against further oxidative injury in tissues and cells following various insults; this occurs by virtue of the anti-inflammatory and antioxidant capacities of CO, biliverdin, and the subsequent metabolite of biliverdin, bilirubin. In line with the findings from the basic research, numerous studies have supported the importance of HO-1 in various clinical diseases, including coronary artery disease, cardiac hypertrophy, diabetes mellitus, ischemic/reperfusion injury, atherosclerosis and cancer. This review provides an overview on the regulation and function of HO-1, ranging from the molecular mechanisms involved to various clinical perspectives. Specifically, there is a focus on the enzyme's role in various cardiovascular diseases.
Wang
Chao-Yung
CY
Second Section of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Chau
Lee-Young
LY
D002318:Cardiovascular Diseases / Q000201:enzymology / Q000209:etiology*; D054377:Chemokine CXCL12 / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D051547:Heme Oxygenase-1