Heme oxygenase in the regulation of vascular biology: from molecular mechanisms to therapeutic opportunities.
Heme oxygenases (HOs) are the rate-limiting enzymes in the catabolism of heme into biliverdin, free iron, and carbon monoxide. Two genetically distinct isoforms of HO have been characterized: an inducible form, HO-1, and a constitutively expressed form, HO-2. HO-1 is a kind of stress protein, and thus regarded as a sensitive and reliable indicator of cellular oxidative stress. The HO system acts as potent antioxidants, protects endothelial cells from apoptosis, is involved in regulating vascular tone, attenuates inflammatory response in the vessel wall, and participates in angiogenesis and vasculogenesis. Endothelial integrity and activity are thought to occupy the central position in the pathogenesis of cardiovascular diseases. Cardiovascular disease risk conditions converge in the contribution to oxidative stress. The oxidative stress leads to endothelial and vascular smooth muscle cell dysfunction with increases in vessel tone, cell growth, and gene expression that create a pro-thrombotic/pro-inflammatory environment. Subsequent formation, progression, and obstruction of atherosclerotic plaque may result in myocardial infarction, stroke, and cardiovascular death. This background provides the rationale for exploring the potential therapeutic role for HO system in the amelioration of vascular inflammation and prevention of adverse cardiovascular outcomes.
Kim
Young-Myeong
YM
Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Kangwon-do, South Korea.
Pae
Hyun-Ock
HO
Park
Jeong Euy
JE
Lee
Yong Chul
YC
Woo
Je Moon
JM
Kim
Nam-Ho
NH
Choi
Yoon Kyung
YK
Lee
Bok-Soo
BS
Kim
So Ri
SR
Chung
Hun-Taeg
HT
D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000378:metabolism / Q000628:therapy*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress; D014657:Vasculitis / Q000201:enzymology* / Q000378:metabolism / Q000628:therapy*
D006419:Heme Oxygenase (Decyclizing)