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Relationship Between Hypertension and Atherosclerosis: From a Viewpoint of the Most Potent Vasoconstrictor Human Urotensin II

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Human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, and its receptor (UT) are involved in etiology of hypertension. In hypertensive patients, U-II induces vasoconstriction in forearm brachial artery infusion studies. Recent studies demonstrated elevated plasma U-II concentrations in patients with hypertension, diabetes mellitus, atherosclerosis, and coronary artery disease. U-II is expressed in endothelial cells, macrophages, macrophagederived 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, and platelets. U-II accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages, and stimulates cell growth and up-regulates type 1 collagen expression in human endothelial cells. U-II also activates NADPH oxidase and plasminogen activator inhibitor-1 in human VSMCs, and stimulates VSMC proliferation with synergistic effects observed when combined with oxidized LDL, reactive oxygen species and serotonin. These findings suggest that U-II plays key roles in accelerating the development of atherosclerosis, and hence coronary artery disease.

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Keywords: Urotensin II; atherosclerosis; coronary artery disease; hypertension; metabolic syndrome

Document Type: Research Article

Affiliations: Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku,Tokyo 142-8555, Japan.

Publication date: 01 August 2006

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  • Current Hypertension Reviews publishes frontier reviews on all the latest advances on hypertension and its related areas e.g. nephrology, clinical care, and therapy. The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all clinicians and researchers in the field of hypertension.
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