Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages
Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages
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DOI：
10.1016/j.bbrc.2008.08.009
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发表时间：
2008-10-24
影响因子：
3.1
通讯作者：
Yamashita, Shizuya
中科院分区：
文献类型：
--
作者：
Tsubakio-Yamamoto, Kazumi;Matsuura, Fumihiko;Yamashita, Shizuya
血浆高密度脂蛋白(HDL)-胆固醇水平与动脉粥样硬化性心血管疾病的风险呈负相关。逆向胆固醇转运（RCT）是动脉粥样硬化的主要保护系统之一，其中HDL颗粒在将来自外周组织的胆固醇运送到肝脏中起着至关重要的作用。近年来，atp结合盒转运体（ABCA1, ABCG1）和清除率受体（SR-BI）已被确定为通过去除泡沫细胞中的胆固醇生成HDL的重要膜受体。脂肪细胞分泌的脂联素（Adiponectin， APN）是抑制动脉粥样硬化的重要分子之一。流行病学研究显示，人类血浆高密度脂蛋白胆固醇和APN浓度呈正相关，但其机制尚未明确。因此，在本研究中，我们研究了APN在RCT中的作用，特别是人单核细胞来源和APN敲除（APN- ko）小鼠巨噬细胞的细胞胆固醇外排。APN分别上调人巨噬细胞中ABCA1的表达。APN治疗也增加了巨噬细胞apoa -1介导的胆固醇外排。此外，LXR α的mRNA表达。APN增加PPAR γ。在APN-KO小鼠中，与野生型小鼠相比，ABCA1、LXRa、PPAR 1和apoa - i介导的胆固醇外排的表达降低。综上所述，APN可能通过激活LXR α和PPAR γ，通过abca1依赖途径增加巨噬细胞apoa - i介导的胆固醇外泄，从而预防动脉粥样硬化。(C) 2008年Elsevier Inc.出版
Plasma high density lipoprotein (HDL)-cholesterol levels are inversely correlated to the risk of atherosclerotic cardiovascular diseases. Reverse cholesterol transport (RCT) is one of the major protective systems against atherosclerosis, in which HDL particles play a crucial role to carry cholesterol derived from peripheral tissues to the liver. Recently, ATP-binding cassette transporters (ABCA1, ABCG1) and scavenger receptor (SR-BI) have been identified as important membrane receptors to generate HDL by removing cholesterol from foam cells. Adiponectin (APN) secreted from adipocytes is one of the important molecules to inhibit the development of atherosclerosis. Epidemiological Studies have revealed a positive correlation between plasma HDL-cholesterol and APN concentrations in humans, although its mechanism has not been clarified. Therefore, in the present study, we investigated the role of APN on RCT, in particular, cellular cholesterol efflux from human monocyte-derived and APN-knockout (APN-KO) mice macrophages. APN up-regulated the expression of ABCA1 in human macrophages, respectively. ApoA-1-mediated cholesterol efflux from macrophages was also increased by APN treatment. Furthermore, the mRNA expression of LXR alpha. and PPAR gamma was increased by APN. In APN-KO mice, the expression of ABCA1, LXRa, PPAR 1, and apoA-I-mediated cholesterol efflux was decreased compared with wild-type mice. In summary, APN might protect against atherosclerosis by increasing apoA-I-mediated cholesterol efflux from macrophages through ABCA1-dependent pathway by the activation of LXR alpha and PPAR gamma. (C) 2008 Published by Elsevier Inc.