CTRP9 通过增强胆固醇外排来减轻泡沫细胞凋亡。
CTRP9 alleviates foam cells apoptosis by enhancing cholesterol efflux.
机构信息
Department of General Medicine, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, 250012, Jinan, Shandong, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China.
Department of Cardiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, 250012, Jinan, Shandong, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, 250012, Jinan, China.
出版信息
Mol Cell Endocrinol. 2021 Feb 15;522:111138. doi: 10.1016/j.mce.2020.111138. Epub 2020 Dec 19.
The apoptosis of foam cells leads to instability of atherosclerotic plaques. This study was designed to explore the protective role of CTRP9 in foam cell apoptosis. In our experiment, CTRP9 alleviated foam cell apoptosis. Meanwhile, CTRP9 upregulated the expression of proteins important for cholesterol efflux, such as LXRα, CYP27A1, ABCG1 and ABCA1, and improved cholesterol efflux in foam cells. Moreover, CTRP9 inhibited Wnt3a and β-catenin expression and β-catenin nuclear translocation in foam cells. In addition, adenovirus overexpression of Wnt3a abolished the effect of CTRP9 on macrophage apoptosis. Mechanistically, the AMPK inhibitor abolished the effect of CTRP9 on foam cell apoptosis, and downregulation of AdipoR1 by siRNA abrogated the activation of AMPK and the effect of CTRP9 on foam cell apoptosis. We concluded that CTRP9 achieved these protective effects on foam cells through the AdipoR1/AMPK pathway.
泡沫细胞的凋亡导致动脉粥样硬化斑块不稳定。本研究旨在探讨 CTRP9 在泡沫细胞凋亡中的保护作用。在我们的实验中，CTRP9 减轻了泡沫细胞的凋亡。同时，CTRP9 上调了胆固醇外排的重要蛋白的表达，如 LXRα、CYP27A1、ABCG1 和 ABCA1，并改善了泡沫细胞中的胆固醇外排。此外，CTRP9 抑制了泡沫细胞中 Wnt3a 和 β-连环蛋白的表达以及 β-连环蛋白的核转位。此外，腺病毒过表达 Wnt3a 消除了 CTRP9 对巨噬细胞凋亡的影响。在机制上，AMPK 抑制剂消除了 CTRP9 对泡沫细胞凋亡的影响，而 siRNA 下调 AdipoR1 消除了 AMPK 的激活和 CTRP9 对泡沫细胞凋亡的作用。我们得出结论，CTRP9 通过 AdipoR1/AMPK 途径对泡沫细胞发挥这些保护作用。
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