[Heme oxygenase and carbon monoxide in the physiology and pathology of the cardiovascular system].
Heme oxygenase (HO) degrades heme to carbon monoxide (CO), ferrous ions, and the bile pigment biliverdin, which is subsequently reduced to the other important bile pigment, bilirubin, by biliverdin reductase. Fe2+ liberated from the heme molecule upregulates ferritin production, and bile pigments are potent endogenous antioxidants. The HO enzyme exists in three isophorms: HO-1 is expressed at low levels under physiological conditions, but is induced by numerous factors, including oxidative stress, inflammation, nitric oxide, an elevated level of substrate, and hypoxia. HO-2 is a constitutive enzyme involved in the baseline production of CO in the cardiovascular and nervous systems, whereas HO-3 is also ubiquitously expressed, but possesses low catalytic activity. Like nitric oxide, CO activates soluble guanylate cyclase and elevates cGMP in target tissues, which dilates blood vessels. It also does this by directly activating potassium channels in vascular smooth muscle cells. In addition, CO inhibits platelet aggregation and proliferation of vascular smooth muscle cells, inhibits apoptosis, and stimulates angiogenesis. Both deficiency, and excess of HO-1 may be involved in the pathogenesis of arterial hypertension. Induction of HO-1 attenuates atherosclerosis and myocardial ischemia-reperfusion injury. Pharmacological and genetic induction of HO-1 as well as the delivery of exogenous CO are promising therapeutic strategies for the treatment of cardiovascular diseases.
Bełtowski
Jerzy
J
Katedra i Zakład Patofizjologii, Akademii Medycznej, w Lublinie. patfiz@asklepios.am.lublin.pl
Jamroz
Anna
A
Borkowska
Ewelina
E
D017209:Apoptosis / Q000502:physiology; D001663:Bilirubin / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000503:physiopathology* / Q000628:therapy*; D016027:Heart Transplantation; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D008565:Membrane Proteins
D008565:Membrane Proteins; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001663:Bilirubin