Heme oxygenase--carbon monoxide signalling pathway as a physiological regulator of vascular smooth muscle cells.

Heme oxygenase (HO) is a microsomal enzyme involved in the degradation of heme and biliverdin and carbon monoxide, the former being subsequently converted to bilirubin by the cytosolic biliverdin reductase. Two isoenzymes transcribed from separate genes have been characterized. The HO-2 isoform is constitutively expressed and is present in high concentration in the brain and testes. In contrast, the HO-1 isoform is ubiquitous, found in large quantities in liver and spleen and can be induced by its own substrate, heme and by a variety of stress-associated agents. Both HO-1 and HO-2 mRNA and protein have been detected in endothelial and smooth muscle cells of arterial and venous blood vessels. Carbon monoxide (CO) from HO catalysis has been identified as an endogenous biological messenger and recent studies suggest its important role in the circulation. Similarly to nitric oxide (NO), CO inhibits platelet aggregation and relaxes blood vessels by activating soluble guanylyl cyclase (sGC) and elevating intracellular levels of cyclic guanosine-3',5'-monophosphate (cGMP). CO is a powerful vasodilator and together with NO may serve as an important modulator of vascular cell function.