title: Urotensin II promotes atherosclerosis in cholesterol-fed rabbits.
abstract: Urotensin II (UII) is a vasoactive peptide composed of 11 amino acids that has been implicated to contribute to the development of cardiovascular disease. The purpose of this study was to investigate whether UII affects the development of atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol diet. Plasma lipids and body weight were measured every 4 weeks. Aortic atherosclerotic lesions along with cellular components, collagen fibers, matrix metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of atherosclerotic plaques was evaluated. UII infusion significantly increased atherosclerotic lesions within the entire aorta by 21% over the control (P = 0.013). Atherosclerotic lesions were increased by 24% in the aortic arch (P = 0.005), 11% in the thoracic aorta (P = 0.054) and 18% in the abdominal aorta (P = 0.035). These increases occurred without changes in plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or body weight. Immunohistochemical staining revealed that macrophages and matrix metalloproteinase-9 were significantly enhanced by 2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up-regulated the expression of vascular cell adhesion protein-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, which was inhibited by the UII receptor antagonist urantide. In conclusion, our results showed that UII promotes the development of atherosclerotic lesions and destabilizes atherosclerotic plaques in cholesterol-fed rabbits.
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Sihai
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Ninghong
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors.forename: Huadong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors.forename: Daxing
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
authors.affiliation: Laboratory for Lipid Metabolism and Atherosclerosis, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China; Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Enqi
authors.initials: E
authors.lastname: Liu
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D001835:Body Weight; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood; D011817:Rabbits; D014579:Urotensins / Q000502:physiology*
chemical_list: D002791:Cholesterol, Dietary; D008055:Lipids; D014579:Urotensins; C029677:urotensin II
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