Anti-Atherogenic Effects of Vaspin on Human Aortic Smooth Muscle Cell/Macrophage Responses and Hyperlipidemic Mouse Plaque Phenotype.
Anti-Atherogenic Effects of Vaspin on Human Aortic Smooth Muscle Cell/Macrophage Responses and Hyperlipidemic Mouse Plaque Phenotype.
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DOI：
10.3390/ijms19061732
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发表时间：
2018-06-11
影响因子：
5.6
通讯作者：
Watanabe T
中科院分区：
文献类型：
--
作者：
Sato K;Shirai R;Yamaguchi M;Yamashita T;Shibata K;Okano T;Mori Y;Matsuyama TA;Ishibashi-Ueda H;Hirano T;Watanabe T
Vaspin（内脏脂肪组织来源的丝氨酸蛋白酶抑制剂）是最近发现的具有胰岛素增敏作用的新型脂肪细胞因子。据报道，冠状动脉疾病患者的血清vaspin水平升高或降低。我们的转化研究旨在评估vaspin在人冠状动脉粥样硬化病变中的表达，及其对人巨噬细胞和人主动脉平滑肌细胞（HASMC）致动脉粥样硬化反应的影响，以及自发性高脂血症Apoe−/−小鼠（一种动脉粥样硬化动物模型）中主动脉粥样硬化病变发展的影响。Vaspin在人冠状动脉粥样硬化斑块内的巨噬细胞/血管平滑肌细胞（VSMCs）中以高水平表达。Vaspin显著抑制人巨噬细胞中核因子κB下调的炎症表型。在人巨噬细胞中，Vaspin显著抑制氧化低密度脂蛋白诱导的泡沫细胞形成，并伴随CD 36和酰基辅酶A：胆固醇酰基转移酶-1下调、ATP结合盒转运蛋白A1和G1以及清道夫受体B类1型上调。Vaspin显著抑制血管紧张素II诱导的迁移和增殖，ERK 1/2和JNK下调，并增加胶原蛋白的产生，磷酸肌醇3-激酶和Akt上调HASMCs。向Apoe-/-小鼠长期输注vaspin可显着抑制主动脉粥样硬化病变的发展，斑块内炎症和巨噬细胞/VSMC比率（斑块不稳定的标志物）显着降低。我们的研究表明，vaspin可防止动脉粥样硬化斑块的形成和不稳定性，并可能成为动脉粥样硬化性心血管疾病的一个新的治疗靶点。
Vaspin (visceral adipose tissue-derived serine protease inhibitor) was recently identified as a novel adipocytokine with insulin-sensitizing effects. Serum vaspin levels are reported either increased or decreased in patients with coronary artery disease. Our translational research was performed to evaluate the expression of vaspin in human coronary atherosclerotic lesions, and its effects on atherogenic responses in human macrophages and human aortic smooth muscle cells (HASMC), as well as aortic atherosclerotic lesion development in spontaneously hyperlipidemic Apoe−/− mice, an animal model of atherosclerosis. Vaspin was expressed at high levels in macrophages/vascular smooth muscle cells (VSMCs) within human coronary atheromatous plaques. Vaspin significantly suppressed inflammatory phenotypes with nuclear factor κB down-regulation in human macrophages. Vaspin significantly suppressed oxidized low-density lipoprotein-induced foam cell formation with CD36 and acyl-coenzyme A: cholesterol acyltransferase-1 down-regulation and ATP-binding cassette transporters A1 and G1, and scavenger receptor class B type 1 up-regulation in human macrophages. Vaspin significantly suppressed angiotensin II-induced migration and proliferation with ERK1/2 and JNK down-regulation, and increased collagen production with phosphoinositide 3-kinase and Akt up-regulation in HASMCs. Chronic infusion of vaspin into Apoe−/− mice significantly suppressed the development of aortic atherosclerotic lesions, with significant reductions of intraplaque inflammation and the macrophage/VSMC ratio, a marker of plaque instability. Our study indicates that vaspin prevents atherosclerotic plaque formation and instability, and may serve as a novel therapeutic target in atherosclerotic cardiovascular diseases.
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影响因子：
8
作者：
Heiker, John T.;Kloeting, Nora;Kovacs, Peter;Kuettner, E. Bartholomeus;Straeter, Norbert;Schultz, Stephan;Kern, Matthias;Stumvoll, Michael;Blueher, Matthias;Beck-Sickinger, Annette G.
通讯作者：
Beck-Sickinger, Annette G.
影响因子：
9.8
作者：
El-Mesallamy, Hala O.;Kassem, Dina H.;Amin, Ashraf I.
通讯作者：
Amin, Ashraf I.
影响因子：
5.3
作者：
Li, Hailing;Peng, Wenhui;Xu, Yawei
通讯作者：
Xu, Yawei
影响因子：
9.3
作者：
Jung CH;Lee MJ;Kang YM;Lee YL;Yoon HK;Kang SW;Lee WJ;Park JY
通讯作者：
Park JY
影响因子：
2.2
作者：
Esteghamati, A.;Mousavizadeh, M.;Nakhjavani, M.
通讯作者：
Nakhjavani, M.