モリ　フミアキ   Mori Fumiaki   森　文章    所属   医学部 医学科（東京女子医科大学病院）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	PSGL-1 expressing CD4 T cells contribute plaque instability in acute coronary syndrome.
掲載誌名	正式名：Circulation 略　 称：Circulation ISSNコード：00097322/15244539
掲載区分	国外
出版社	American Heart Association, Inc.
巻・号・頁	124(21),pp.Abstract 15412
著者・共著者	SATO Kayoko†, FUKUSHIMA Keiko, FUTASE Atsuko, MORI Fumiaki, SAWABE Motoji, HAGIWARA Nobuhisa
発行年月	2018/05
概要	Background: Adhesion molecules have essential roles for the development of atherosclerosis. We examined whether PSGL-1 expressing CD4 T cells in acute coronary syndrome (ACS) contribute to plaque instability. Methods and Results: CD4 T cells were isolated from the peripheral blood (PB) of 36 ACS patients (AMI=23, UAP=13) and 24 healthy controls (NC). CD4 T cells from ACS strongly expressed PSGL-1 and integrin β2 (P<0.05 and P<0.05, respectively), but not L-selectin and integrin αM by FACS. We investigated the thrombus-aspirating device samples (n=22) and CD4 T cells derived from both the coronary artery (CA) and PB from the same ACS patients. We confirmed culprit lesion contained abundant PSGL-1+CD4+ T cells (P<0.001), but not integrin β2+CD4+ T cells by FACS. In addition, immunohistochemistry revealed that many PSGL-1+CD4+ T cells were in the plaques and thrombus from the culprit lesion. To investigate whether PSGL-1+CD4+ T cells from ACS could bind to P-selectin or E-selectin, we analyzed PSGL-1+CD4+ T cells by selectin binding assay. PSGL-1+CD4+ T cells strongly bound to both P-selectin and E-selectin after TCR triggering. Furthermore, apoptosis assay of endothelial cells (EC) showed that PSGL-1+CD4+ T cells from CA strongly induced EC apoptosis compared to those from PB (P<0.01). In addition, EC apoptosis correlated with the expression of PSGL-1 (R=0.788, P<0.03), and was inhibited by anti-PSGL-1 Ab (P<0.05). Finally, we investigated the mechanism of PSGL-1+CD4+ T cells induced EC apoptosis. EC co-cultured with PSGL-1+CD4+ T cells from ACS strongly expressed PARP by immunohistochemistry and active caspase-3 by FACS. Conclusions: From these results, we demonstrated that PSGL-1 expressing CD4 T cells participate directly in the acceleration of plaque instability in ACS.
DOI	doi:10.1253/circj.CJ-17-1270