Urotensin-II and cardiovascular remodeling.
Urotensin-II (U-II), a cyclic undecapeptide, and its receptor, UT, have been linked to vascular and cardiac remodeling. In patients with coronary artery disease (CAD), it has been shown that U-II plasma levels are significantly greater than in normal patients and the severity of the disease is increased proportionally to the U-II plasma levels. We showed that U-II protein and mRNA levels were significantly elevated in the arteries of patients with coronary atherosclerosis in comparison to healthy arteries. We observed U-II expression in endothelial cells, foam cells, and myointimal and medial vSMCs of atherosclerotic human coronary arteries. Recent studies have demonstrated that U-II acts in synergy with mildly oxidized LDL inducing vascular smooth muscle cell (vSMC) proliferation. Additionally, U-II has been shown to induce cardiac fibrosis and cardiomyocyte hypertrophy leading to cardiac remodeling. When using a selective U-II antagonist, SB-611812, we demonstrated a decrease in cardiac dysfunction including a reduction in cardiomyocyte hypertrophy and cardiac fibrosis. These findings suggest that U-II is undoubtedly a potential therapeutic target in treating cardiovascular remodeling.
Papadopoulos
Panayiota
P
Division of Cardiology, Montreal General Hospital, McGill University Health Center, Montreal, Quebec, Canada.
Bousette
Nicolas
N
Giaid
Adel
A
D002319:Cardiovascular System / Q000033:anatomy & histology / Q000378:metabolism; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D013449:Sulfonamides / Q000378:metabolism; D014579:Urotensins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000502:physiology*; D000096926:Benzenesulfonamides
D013449:Sulfonamides; D014579:Urotensins; C513816:SB-611812; D000096926:Benzenesulfonamides; C029677:urotensin II