Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Original Article
Oxidized High-Density Lipoprotein Induces the Proliferation and Migration of Vascular Smooth Muscle Cells by Promoting the Production of ROS
Yan WangLiang JiRengui JiangLemin ZhengDonghui Liu
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JOURNALS FREE ACCESS

2014 Volume 21 Issue 3 Pages 204-216

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Abstract

Aim: As the major atheroprotective particle in plasma, high-density lipoprotein(HDL) is oxidized during atherosclerotic processes. Oxidized HDL(ox-HDL) may lose its cardioprotective properties and develop a proinflammatory and proatherogenic phenotype. The proliferation and migration of vascular smooth muscle cells(VSMCs) play a crucial role in atherogenesis. However, the influence of ox-HDL on VSMC proliferation and migration remains poorly understood.
Methods: VSMCs were treated with native HDL(N-HDL) or ox-HDL at varying concentrations for different time intervals and used in several analyses. The degree of cell proliferation was assayed using CCK-8 kits. The level of cell migration was determined using a Transwell chamber and scratch-wound assay. The presence of intracellular reactive oxygen species(ROS) was detected based on ROS-mediated 2’,7’-dichlorofluorescein fluorescence. The activation of NADPH oxidase was measured in terms of the Rac1 activity and NADP/NADPH ratio.
Results: Compared to N-HDL, ox-HDL significantly promoted VSMC proliferation and migration in a dose-dependent manner. In addition, ox-HDL remarkably activated NADPH oxidase and enhanced ROS generation in the VSMCs. Diphenyleneiodonium chloride, an inhibitor of NADPH oxidase, and N-acetylcysteine, a ROS scavenger, efficiently inhibited the ROS production triggered by ox-HDL and subsequently blocked the proliferating and migrating effects of ox-HDL in the VSMCs.
Conclusions: Ox-HDL significantly induces VSMC proliferation and migration by promoting NADPH oxidase activation and ROS production. Furthermore, the inhibition of NADPH oxidase and ROS generation blocks the proliferation and migration of VSMCs induced by ox-HDL. These proliferating and migrating effects of ox-HDL are closely related to its proinflammatory and proatherogenic roles.

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この記事はクリエイティブ・コモンズ [表示 - 非営利 - 継承 4.0 国際]ライセンスの下に提供されています。
https://creativecommons.org/licenses/by-nc-sa/4.0/deed.ja
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