Key result
UII gene deletion or treatment with the UT antagonist SB657510A significantly reduced weight gain, visceral fat, hyperlipidemia, and atherosclerosis progression in mice (P<0.05).
Why the study?
Does UII gene deletion or UT blockade ameliorate experimental atherosclerosis and metabolic sequelae in mice?
Does UII gene deletion or UT blockade ameliorate experimental atherosclerosis and metabolic sequelae in mice?
p-value: p=<0.05
Genetic deletion or pharmacological blockade of the Urotensin II pathway attenuates atherosclerosis and metabolic syndrome precursors in mice, suggesting a potential novel therapeutic target.
OBJECTIVE: Urotensin II (UII) is a potent vasoactive peptide that binds to the urotensin receptor-coupled receptor-14 (known as UT) and exerts a wide range of actions in humans and experimental animals. We tested the hypothesis that UII gene deletion or UT blockade ameliorate experimental atherosclerosis. METHODS AND RESULTS: We observed a significant reduction in weight gain, visceral fat, blood pressure, circulating plasma lipids, and proatherogenic cytokines and improvement of glucose tolerance in UII knockout mice compared with wild type (P<0.05). Deletion of UII after an apolipoprotein E knockout resulted in a significant reduction in serum cytokines, adipokines, and aortic atherosclerosis compared with apolipoprotein E knockout mice. Similarly, treatment of apolipoprotein E knockout mice fed on high-fat diet with the UT antagonist SB657510A reduced weight gain, visceral fat, and hyperlipidemia and improved glucose tolerance (P<0.05) and attenuated the initiation and progression of atherosclerosis. The UT antagonist also decreased aortic extracellular signal-regulated kinase 1/2 phosphorylation and oxidant formation and serum level of cytokines (P<0.05). CONCLUSIONS: These findings demonstrate for the first time the role of UII gene deletion in atherosclerosis and suggest that the use of pharmaceutical agents aimed at blocking the UII pathway may provide a novel approach in the treatment of atherosclerosis and its associated precursors such as obesity, hyperlipidemia, diabetes mellitus, and hypertension.
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You et al. (2012) studied Atherosclerosis and metabolic sequelae. UII gene deletion or UT antagonist SB657510A vs. Wild type mice or untreated apolipoprotein E knockout mice was evaluated on Weight gain, visceral fat, blood pressure, circulating plasma lipids, proatherogenic cytokines, glucose tolerance, and atherosclerosis (p=<0.05). UII gene deletion or treatment with the UT antagonist SB657510A significantly reduced weight gain, visceral fat, hyperlipidemia, and atherosclerosis progression in mice (P<0.05).
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