1: Vasc Med. 2002 Aug;7(3):195-202. 

Carbon monoxide and bile pigments: surprising mediators of vascular function.

Durante W.

Department of Medicine, Baylor College of Medicine, and Veterans Affairs Medical
Center, Houston, TX 77030, USA. wdurante@bcm.tmc.edu

Heme oxygenase (HO) catalyzes the degradation of heme to CO, iron, and
biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme
biliverdin reductase. Although long considered irrelevant byproducts of heme
catabolism, recent studies indicate that CO and the bile pigments biliverdin and
bilirubin may play an important physiological role in the circulation. The
release of CO by vascular cells may modulate blood flow and blood fluidity by
inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet
aggregation. CO may also maintain the integrity of the vessel wall by directly
blocking vascular cell apoptosis and by inhibiting the release of pro-apoptotic
inflammatory cytokines from the vessel wall. These effects of CO are mediated
via multiple pathways, including activation of soluble guanylate cyclase,
potassium channels, p38 mitogen-activated protein kinase, or inhibition of
cytochrome P450. In addition, the release of bile pigments may serve to sustain
vascular homeostasis by protecting vascular cells from oxidative stress and by
inhibiting the adhesion and infiltration of leukocytes into the vessel wall.
Induction of HO-1 gene expression and the subsequent release of CO and bile
pigments are observed in numerous vascular disorders and may provide an
important adaptive mechanism to preserve homeostasis at sites of vascular
injury. Thus, the HO-catalyzed formation of CO and bile pigments by vascular
cells may function as a critical endogenous vasoprotective system. Moreover,
pharmacological or genetic approaches targeting HO-1 to the vessel wall may
represent a novel therapeutic approach in treating vascular disease.

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PMID: 12553743 [PubMed - indexed for MEDLINE]