Heme oxygenase-1 and cardiovascular disease.
Heme oxygenase (HO)-1 is the inducible isoform of the first and rate-controlling enzyme of heme degradation. HO-1 is up-regulated by a host of oxidative stress stimuli and has potent cytoprotective and anti-inflammatory functions via decreasing tissue levels of the prooxidant heme along with production of bilirubin and the signaling gas carbon monoxide. This review deals with recent findings that highlight the emerging significance of HO-1 in cardiovascular disease. Evidence is presented on how heme and various oxidative stress stimuli may cause endothelial cell dysfunction and how HO-1 may counteract the detrimental effects of oxidative stress in the endothelium. Recent advances in the understanding of the role of endothelial HO-1 for the regulation of the inflammatory response are summarized, including the modulation of leukocyte recruitment and transmigration through the endothelial barrier. Furthermore, experimental evidence from various cell culture and animal models is discussed which suggests an association of HO-1 with the complex sequence of events that cause atherosclerosis. In the second part of the review we present potential strategies that apply HO-1 as a therapeutic target in the treatment of cardiovascular disease. Specific inducers of HO-activity which may ultimately lead to the development of clinically relevant pharmacological applications are introduced.
Immenschuh
S
S
Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University Giessen, Giessen, Germany. Stephan.Immenschuh@immunologie.med.uni-giessen.de
Schröder
H
H
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology; D001663:Bilirubin / Q000378:metabolism; D019256:Cadmium Chloride / Q000494:pharmacology / Q000627:therapeutic use; D002248:Carbon Monoxide / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D004789:Enzyme Activation; D006418:Heme / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology; D020033:Protein Isoforms
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020033:Protein Isoforms; D006418:Heme; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D019256:Cadmium Chloride; D001663:Bilirubin