Human Urotensin II and Metabolic Syndrome

Author(s): Takuya Watanabe, Tomoko Kanome, Toshiaki Suguro, Akira Miyazaki.

Journal Name: Vascular Disease Prevention

Volume 3 , Issue 2 , 2006

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Abstract:

Human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, and its receptor (UT) are involved in atherosclerosis. U-II is expressed in endothelial cells, macrophages, macrophage-derived foam cells, and myointimal and medial vascular smooth muscle cells (VSMCs) of atherosclerotic human coronary arteries. UT receptors are present in VSMCs of human coronary arteries, thoracic aorta and cardiac myocytes. Lymphocytes are the most active producers of U-II, whereas monocytes and macrophages are the major cell types expressing UT receptors, with relatively little receptor expression in foam cells, lymphocytes, human carotid arteries or aorta. Peripheral infusion of U-II causes vasoconstriction in the human forearm, and U-II also stimulates VSMC proliferation and shows synergistic interactions with oxidised LDL, hydrogen peroxide and serotonin. U-II also accelerates foam cell formation by up-regulation of acylcoenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages, up-regulates type 1 collagen expression and down-regulates matrix metalloproteinase-1 expression in human endothelial cells, and activates NADPH oxidase and plasminogen activator inhibitor-1 in human VSMCs, leading to progression of atherosclerotic plaque. Clinical studies demonstrated elevated plasma U-II concentrations in patients with hypertension or diabetes mellitus, and positive correlations with systolic and diastolic blood pressure, body weight and fasting plasma glucose levels, while experimental studies indicated that U-II inhibits glucose-induced insulin release from pancreatic β cells in rats, promotes food intake in mice and hyperlipidaemia by channelling glucose to free fatty acid synthesis in fish. These findings suggest that U-II plays key roles in metabolic syndrome.

Keywords: Urotensin II, metabolic syndrome, atherosclerosis, hypertension, diabetes mellitus, hyperlipidemia, obesity, coronary artery disease

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Article Details

VOLUME: 3
ISSUE: 2
Year: 2006
Page: [91 - 98]
Pages: 8
DOI: 10.2174/1567270010603020091
Price: $58