Emerging roles of urotensin-II in cardiovascular disease.
Urotensin-II (UII) is a highly potent endogenous peptide within the cardiovascular system. Through stimulation of Galphaq-coupled UT receptors, UII mediates contraction of vascular smooth muscle and endothelial-dependent vasorelaxation, and positive inotropy in human right atrium and ventricle. A pathogenic role of the UT receptor system is emerging in cardiovascular disease states, with evidence for up-regulation of the UT receptor system in patients with congestive heart failure (CHF), pulmonary hypertension, cirrhosis and portal hypertension, and chronic renal failure. In vitro and in vivo studies show that under pathophysiological conditions, UII might contribute to cardiomyocyte hypertrophy, extracellular matrix production, enhanced vasoconstriction, vascular smooth muscle cell hyperplasia, and endothelial cell hyper-permeability. Single nucleotide polymorphisms of the UII gene may also impart a genetic predisposition of patients to diabetes. Therefore, the UT receptor system is a potential therapeutic target in the treatment of cardiac, pulmonary, and renal diseases. UT receptor antagonists are currently being developed to prevent and/or reverse the effects of over-activated UT receptors by the endogenous ligand. This review describes UII peptide and converting enzymes, and UT receptors in the cardiovascular system, focusing on pathophysiological roles of UII in the heart and blood vessels.
Vascular Biology Laboratory, Department of Medicine, The University of Queensland, Brisbane, The Prince Charles Hospital, Pathology Building, Rode Road, Ground Floor, Room 3, Chermside 4032, Queensland, Australia. russell@medicine.uq.edu.au
Fraser D
FD
Russell
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000503:physiopathology; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000503:physiopathology; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D014579:Urotensins / Q000378:metabolism / Q000502:physiology*
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C029677:urotensin II