A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis.
A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis.
复制标题
DOI：
--
复制
发表时间：
2001
期刊：
影响因子：
16
通讯作者：
A. Chawla;W. Boisvert;Chih‐Hao Lee;B. Laffitte;Y. Barak;S. Joseph;D. Liao;Laszlo Nagy;Peter A.
中科院分区：
文献类型：
--
作者：
A. Chawla;W. Boisvert;Chih‐Hao Lee;B. Laffitte;Y. Barak;S. Joseph;D. Liao;Laszlo Nagy;Peter A.
以前的工作表明，PPARγ参与调节CD36的表达和巨噬细胞对氧化低密度脂蛋白(OxLDL)的摄取。我们在这里提供的证据表明，除了脂质摄取，PPAR伽马还调节胆固醇外流的一条途径。PPARγ通过核受体LXRα介导的转录级联反应诱导巨噬细胞ABCA1的表达和胆固醇的清除。PPARγ的配体激活导致LXRα的初级诱导和ABCA1的耦合诱导。将PPARγ缺失的骨髓移植到LDLR-/-小鼠体内后，动脉粥样硬化的发生率显著增加，这与调节LXRα和ABCA1表达在体内具有保护性的假设是一致的。因此，我们认为PPAR伽马通过ABCA1协调对oxLDL的复杂生理反应，包括颗粒摄取、加工和胆固醇去除。
Previous work has implicated PPAR gamma in the regulation of CD36 expression and macrophage uptake of oxidized LDL (oxLDL). We provide evidence here that in addition to lipid uptake, PPAR gamma regulates a pathway of cholesterol efflux. PPAR gamma induces ABCA1 expression and cholesterol removal from macrophages through a transcriptional cascade mediated by the nuclear receptor LXR alpha. Ligand activation of PPAR gamma leads to primary induction of LXR alpha and to coupled induction of ABCA1. Transplantation of PPAR gamma null bone marrow into LDLR -/- mice results in a significant increase in atherosclerosis, consistent with the hypothesis that regulation of LXR alpha and ABCA1 expression is protective in vivo. Thus, we propose that PPAR gamma coordinates a complex physiologic response to oxLDL that involves particle uptake, processing, and cholesterol removal through ABCA1.