Urotensin II promotes atherosclerosis in cholesterol-fed rabbits.
Urotensin II promotes atherosclerosis in cholesterol-fed rabbits.
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DOI：
10.1371/journal.pone.0095089
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liu E
中科院分区：
文献类型：
--
作者：
Li Y;Zhao S;Wang Y;Chen Y;Lin Y;Zhu N;Zheng H;Wu M;Cheng D;Li Y;Bai L;Fan J;Liu E
尿紧张素II （UII）是一种由11种氨基酸组成的血管活性肽，与心血管疾病的发展有关。本研究的目的是探讨UII是否影响胆固醇喂养家兔动脉粥样硬化的发展。将UII通过微型渗透泵注入饲喂高胆固醇饮食的雄性日本大白兔体内，持续16周。每4周测定一次血脂和体重。检查主动脉粥样硬化病变及细胞成分、胶原纤维、基质金属蛋白酶-1、-9。评估动脉粥样硬化斑块易损指数。与对照组相比，UII输注显著增加了整个主动脉内动脉粥样硬化病变21% （P = 0.013）。主动脉弓动脉粥样硬化病变增加24% (P = 0.005)，胸主动脉增加11% (P = 0.054)，腹主动脉增加18% （P = 0.035）。这些增加发生在血浆总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯或体重水平没有变化的情况下。免疫组化染色显示，UII组巨噬细胞和基质金属蛋白酶-9显著增加2.2倍和1.6倍。体外研究表明，UII可上调人脐静脉内皮细胞中血管细胞粘附蛋白-1和细胞间粘附分子-1的表达，而UII受体拮抗剂urantide可抑制这种表达。总之，我们的研究结果表明，在胆固醇喂养的家兔中，UII促进了动脉粥样硬化病变的发展，并破坏了动脉粥样硬化斑块的稳定。
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.
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