caa a22 4500 606236589 CHVBK 20210128101248.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s11010-014-2272-3 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2272-3 Mesenchymal stem cells alleviate atherosclerosis by elevating number and function of CD4+CD25+FOXP3+ regulatory T-cells and inhibiting macrophage foam cell formation [Elektronische Daten] [Zhi Wang, Chong Wang, Xiao Li, Gao Feng, Hong Zhu, Yan Ding, Xue Jiang] Atherosclerosis is a chronic inflammatory disease characterized by the formation of plaques inside arteries, leading to narrowing and blockage. Potential therapeutic strategies include expanding the population of regulatory T-cells (Tregs) to enhance atheroprotective immunity, and inhibiting the formation of macrophage foam cells. Here, we studied the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on atherosclerotic plaque formation in Apolipoprotein E−/− (ApoE-KO) mice, and elucidated the underlying mechanism. BM-MSCs isolated from 4week-old ApoE-KO mice were evaluated by flow cytometry for expression of MSC-specific markers. Thirty eight week-old ApoE-KO mice were randomly divided into three experimental groups (n=10 per group): 1. MSC group—received BM-MSCs intravenously; 2. Vehicle group—received DMEM; 3. Control group—did not receive any treatment. Administration of MSCs resulted in a marked decrease in the size of atherosclerotic plaques 3months after treatment. In addition, the number and function of CD4+CD25+FOXP3+ regulatory T-cells (Tregs) in cultured splenocytes, and the expression of FOXP3 at both mRNA and protein levels, was significantly increased in the MSC group. In vitro experiments further indicated that the formation of macrophage foam cells was inhibited by treatment with MSCs, accompanied by a significant downregulation in CD36 and scavenger receptor A (SRA). Our findings suggest that MSCs play an atheroprotective role by enhancing the number and function of Tregs and inhibiting the formation of macrophage foam cells. Hence, administration of MSCs to atherosclerotic patients might have significant clinical benefits. Springer Science+Business Media New York, 2014 Mesenchymal stem cells nationallicence Atherosclerotic plaque nationallicence CD4+CD25+FOXP3+ regulatory T-cells nationallicence Macrophage foam cell nationallicence Wang Zhi Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, People's Republic of China aut Wang Chong Department of Cardiology, Taihe Hospital, Hubei University of Medicine, 442000, Shiyan, Hubei, People's Republic of China aut Li Xiao Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, People's Republic of China aut Feng Gao Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, People's Republic of China aut Zhu Hong Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, People's Republic of China aut Ding Yan Hubei Provincial Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, 442000, Shiyan, People's Republic of China aut Jiang Xue Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 163-172 0300-8177 400:1-2<163 2015 400 11010 https://doi.org/10.1007/s11010-014-2272-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2272-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wang Zhi Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, People's Republic of China aut NATIONALLICENCE 700 1- Wang Chong Department of Cardiology, Taihe Hospital, Hubei University of Medicine, 442000, Shiyan, Hubei, People's Republic of China aut NATIONALLICENCE 700 1- Li Xiao Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, People's Republic of China aut NATIONALLICENCE 700 1- Feng Gao Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, People's Republic of China aut NATIONALLICENCE 700 1- Zhu Hong Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, People's Republic of China aut NATIONALLICENCE 700 1- Ding Yan Hubei Provincial Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, 442000, Shiyan, People's Republic of China aut NATIONALLICENCE 700 1- Jiang Xue Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 163-172 0300-8177 400:1-2<163 2015 400 11010