A role for urotensin II in restenosis following balloon angioplasty: use of a selective UT receptor blocker

Rakowski, Ewa; Hassan, Ghada S.; Dhanak, Dashyant; Ohlstein, Eliot H.; Douglas, Stephen A.; Giaid, Adel

doi:10.1016/j.yjmcc.2005.07.002

Cited by 53 publications

(38 citation statements)

References 33 publications

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“…The mitogenic role of U-II in SMCs is in accordance with our recent study that showed significantly increased U-II expression in the neointima of rat carotid artery [37]. Specifically, balloon-mediated injury in the carotid artery of the rat led to a substantial increase in intima: media thickness ratio, and this was associated with significantly increased U-II expression.…”

Section: Atherosclerosissupporting

confidence: 90%

Urotensin-II and cardiovascular diseases

Bousette¹,

Giaid

2006

Current Science Inc

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Urotensin-II (U-II) is a vasoactive factor with pleiotropic effects. U-II exerts its activity by binding to a G-protein-coupled receptor termed UT. U-II and its receptor are highly expressed in the cardiovascular system. Increased U-II plasma levels have been reported in patients with cardiovascular disease of varying etiologies. We and others have shown that U-II and UT expression is elevated in both clinical and experimental heart failure and atherosclerosis. U-II induces cardiac fibrosis by increasing fibroblast collagen synthesis. In addition, U-II induces cardiomyocyte hypertrophy and increased vascular smooth muscle cell proliferation. We have shown that U-II antagonism using a selective U-II blocker, SB-611812 reduces neointimal thickening and increases lumen diameter in a rat restenosis model of carotid artery angioplasty. These findings suggest an important role for U-II in cardiovascular dysfunction and remodeling.

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Section: Atherosclerosissupporting

confidence: 90%

Urotensin-II and cardiovascular diseases

Bousette¹,

Giaid

2006

Current Science Inc

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“…The levels of U-II and UT expression are up-regulated by lipopolysaccaride and inflammatory cytokines, such as IL (interleukin)-6 and -1β, IFN-γ (interferon-γ ) and TNF-α (tumour necrosis factor-α) [42,43]. The expression of U-II in the vascular wall is also increased by hypoxia [44] and mechanical stimuli, such as balloon injury [45], but not by either pressure load or shear stress [46].…”

Section: Discussionmentioning

confidence: 99%

Increased plasma urotensin-II levels are associated with diabetic retinopathy and carotid atherosclerosis in Type 2 diabetes

et al. 2008

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Human U-II (urotensin-II), the most potent vasoconstrictor peptide identified to date, is associated with cardiovascular disease. A single nucleotide polymorphism (S89N) in the gene encoding U-II (UTS2) is associated with the onset of Type 2 diabetes and insulin resistance in the Japanese population. In the present study, we have demonstrated a relationship between plasma U-II levels and the progression of diabetic retinopathy and vascular complications in patients with Type 2 diabetes. Eye fundus, IMT (intima-media thickness) and plaque score in the carotid artery, BP (blood pressure), FPG (fasting plasma glucose), HbA(1c) (glycated haemoglobin), U-II, angiogenesis-stimulating factors, such as VEGF (vascular endothelial growth factor) and heregulin-beta(1), and lipid profiles were determined in 64 patients with Type 2 diabetes and 24 non-diabetic controls. FPG, HbA(1c) and VEGF levels were significantly higher in patients with Type 2 diabetes than in non-diabetic controls. Diabetes duration, insufficient glycaemic and BP control, plasma U-II levels, IMT, plaque score and nephropathy grade increased significantly across the subjects as follows: non-diabetic controls, patients with Type 2 diabetes without retinopathy (group N), patients with Type 2 diabetes with simple (background) retinopathy (group A) and patients with Type 2 diabetes with pre-proliferative and proliferative retinopathy (group B). The prevalence of obesity and smoking, age, low-density lipoprotein, triacylglycerols (triglycerides) and heregulin-beta(1) were not significantly different among the four groups. In all subjects, U-II levels were significantly positively correlated with IMT, FPG, and systolic and diastolic BP. Multiple logistic regression analysis revealed that, of the above parameters, U-II levels alone had a significantly independent association with diabetic retinopathy. In conclusion, the results of the present study provide the first evidence that increased plasma U-II levels may be associated with the progression of diabetic retinopathy and carotid atherosclerosis in patients with Type 2 diabetes.

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“…Treatment with ACT-058362 increased insulin release from the pancreas and slowed the increase in glycemia and serum lipids, and delayed the development of proteinuria and renal damage by increasing renal blood flow in streptozotocin-induced diabetic rats (110). Our recent study (18) (85). In rats with congestive heart failure induced by ligating the left coronary artery, treatment with SB-611812 at 30 mg/kg/ day for 8 weeks significantly reduced the mortality by 75%, and significantly improved cardiac function and cardiac remodeling (113).…”

Section: Therapeuticsmentioning

confidence: 90%