Inflammatory Cell–Derived MYDGF Attenuates Endothelial LDL Transcytosis to Protect Against Atherogenesis

作者：Jinling Xu, Huaxing Ma, Lingfeng Shi, Hui Zhou, Yangyang Cheng, Jiayue Tong, Biying Meng, Xiaoli Xu, Kaiyue He, Sheng Ding, Jiajia Zhang, Ling Yue, Guangda Xiang · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2023 · DOI：10.1161/atvbaha.123.319905 · 被引用次数：20 · 研究领域：Immune cells in cancer、Caveolin-1 and cellular processes、FOXO transcription factor regulation

BACKGROUND: Inflammation contributes to the pathogenesis of atherosclerosis. But little is known about the potential benefits of inflammatory cells to atherosclerosis. The aim of this study was to investigate the function of inflammatory cells/endothelium axis and determine whether and how inflammatory cell–derived MYDGF (myeloid-derived growth factor) inhibited endothelial LDL (low-density lipoprotein) transcytosis. METHODS: In in vivo experiments, both loss- and gain-of-function strategies were used to evaluate the effect of inflammatory cell–derived MYDGF on LDL transcytosis. We generated monocyte/macrophage-targeted MYDGF-null mice on an Ldlr (LDL receptor) −/− background in the loss-of-function strategy and restored the inflammatory cell–derived MYDGF by bone marrow transplantation and inflammatory cell–specific overexpression of MYDGF mice model in the gain-of-function strategy. In in vitro experiments, coculture experiments between primary mouse aortic endothelial cells and macrophages and mouse aortic endothelial cells supplemented with or without recombinant MYDGF were conducted. RESULTS: Inflammatory cell–derived MYDGF deficiency aggravated endothelial LDL transcytosis, drove LDL uptake by artery wall, and thus exacerbated atherosclerosis in vivo. Inflammatory cell–derived MYDGF restoration by bone marrow transplantation and inflammatory cell MYDGF overexpression alleviated LDL transport across the endothelium, prevented LDL accumulation in the subendothelial space,...