1: J Cell Physiol. 2003 Jun;195(3):373-82. 

Heme oxygenase-1 in growth control and its clinical application to vascular
disease.

Durante W.

Houston VA Medical Center and Department of Medicine, Baylor College of
Medicine, Houston, Texas 77030, USA. wdurante@bcm.tmc.edu

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. Copyright 2003 Wiley-Liss, Inc.

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PMID: 12704646 [PubMed - indexed for MEDLINE]