Heme oxygenase-1 in growth control and its clinical application to vascular disease.
Heme oxygenase-1 (HO-1) catalyzes the degradation of heme to carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although interest in HO-1 originally centered on its heme-degrading function, recent findings indicate that HO-1 exerts other biologically important actions. Emerging evidence suggests that HO-1 plays a critical role in growth regulation. Deletion of the HO-1 gene or inhibition of HO-1 activity results in growth retardation and impaired fetal development, whereas HO-1 overexpression increases body size. Although the mechanisms responsible for the growth promoting properties of HO-1 are not well established, HO-1 can indirectly influence growth by regulating the synthesis of growth factors and by modulating the delivery of oxygen or nutrients to specific target tissues. In addition, HO-1 exerts important effects on critical determinants of tissue size, including cell proliferation, apoptosis, and hypertrophy. However, the actions of HO-1 are highly variable and may reflect a role for HO-1 in maintaining tissue homeostasis. Considerable evidence supports a crucial role for HO-1 in blocking the growth of vascular smooth muscle cells (SMCs). This antiproliferative effect of HO-1 is mediated primarily via the release of CO, which inhibits vascular SMC growth via multiple pathways. Pharmacologic or genetic approaches targeting HO-1 or CO to the blood vessel wall may represent a promising, novel therapeutic approach in treating vascular proliferative disorders.
Durante
William
W
Houston VA Medical Center and Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. wdurante@bcm.tmc.edu
D017209:Apoptosis; D002455:Cell Division; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors* / Q000502:physiology*; D051547:Heme Oxygenase-1; D006801:Humans; D006984:Hypertrophy / Q000209:etiology; D008565:Membrane Proteins; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D014652:Vascular Diseases / Q000628:therapy*
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1