期刊：
Journal of Lipid Research,2018年59(7):1081-1083 ISSN：0022-2275
通讯作者：
Yin, Kai
作者机构：
[Chen, Hainan; Yin, Kai] Research Lab for Clinical & Translational Medicine, Medical School, and Institute of Cardiovascular Disease, Key Laboratory Atherosclerology of Hunan Province;University of South China;Hengyang 421001, China;[Chen, Hainan; Yin, Kai] University of South China;[Chen, Hainan; Yin, Kai] Hengyang 421001, China
通讯机构：
[Yin, Kai] U;Research Lab for Clinical and Translational Medicine, Medical School, Institute of Cardiovascular Disease, Key Laboratory Atherosclerology of Hunan Province, University of South China, Hengyang, China
摘要：
Objective: Transforming growth factor β1 (TGF-β1) is the major cytokine for stimulating endothelial cells (ECs) to transdifferentiate to mesenchymal cells (MCs) in the process known as endothelial-to-mesenchymal transition (EndMT). Recently, TGF-β1-induced EndMT has been implicated in the pathogenesis of atherosclerosis (AS). It has been identified that apolipoprotein A1 (ApoA-I) obstructs TGF-β1-induced endothelial dysfunction, providing a protective effect for ECs and also anti-AS activity. However, the exact role of ApoA-I in TGF-β1-induced EndMT is not clear. In this study, we aimed to investigate whether ApoA-I can modulate TGF-β1-induced EndMT in human coronary artery ECs (HCAECs). Methods and Results: The HCAECs were treated with TGF-β1 with or without ApoA-I. Morphological changes in HCAECs and the expression of EndMT-related markers were evaluated. HCAECs treated with TGF-β1 were found to transform to MC morphology, with inconspicuous expression of EC markers such as vascular endothelial cadherin and CD31, and conspicuous expression of fibroblast-specific protein 1 (FSP-1) and α-smooth muscle actin. The treatment of HCAECs with ApoA-I inhibited the TGF-β1-induced EndMT, and elevated expression of EC markers was observed but reduced expression of MC markers. Moreover, ApoA-I impeded the expression level of Slug and Snail, crucial transcriptional factors of EndMT, and it inhibited the TGF-β1-induced phosphorylation of Smad2 and Smad3 which affected the EC morphology. In addition, the knockdown of ABCA1 by RNA interference eliminated the inhibition effect of ApoA-I on TGF-β1-induced EndMT. Conclusions: Our findings revealed a novel mechanism for the ApoA-I protective effect on endothelium function via the inhibition of TGF-β1-induced EndMT. This might provide new insights for developing strategies for modulating AS and vascular remodeling.
摘要：
Endothelial-to-mesenchymal transition (EndMT) is a complex biological process in which endothelial cells lose their specific markers and acquire a mesenchymal or myofibroblastic phenotype. Similar to epithelial-to-mesenchymal transition (EMT), EndMT can be induced by multiple stimulants such as cytokines and metabolic factors that play crucial roles in the development of the cardiovascular system. Recent studies have demonstrated that EndMT may play a significant role in the pathogenesis of cardiovascular diseases (CVDs), and may represent a novel therapeutic target for cardiovascular remodeling and fibrotic disorders. The exact molecular mechanisms involved in cardiovascular pathogenesis that occur as a result of EndMT, however, are not fully explained. In this review, we reveal the multiple intercellular mechanisms of EndMT including stimulants, signaling pathways, and seek to explore the relationship between this biological process, cardiovascular system development, and CVDs that may lead to new therapeutic strategies for the treatment of CVDs.
作者机构：
[Wen C.; Juling F.; Hui Z.] Department of Diagnostics, University of South China, Hengyang, 421001, China;[Lei Z.] Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China;[Di X.; Kai Y.] Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, 421001, China
通讯机构：
[Kai, Y.] I;Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, China
作者机构：
[Xiaowang Liu; Jian Tu; Ping Yu; Lei Xiang; Weike Ding; Kaiqiang Lu; Xiaoyong Lei; Linxi Chen] Institute of Pharmacy and Pharmacology,Learning Key Laboratory for Pharmacoproteomics,University of South China,Hengyang 421001,China;[Zhigang Zhou; Kai Yin] Medical college,University of South China,Hengyang 421001,China;[Zhigang Zhou] the First Affiliated Hospital,University of South China,Hengyang 421001,China
