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작성일 : 20-07-29 20:48
논문번호 93
논문제목(영문) A rapamycin derivative, biolimus, preferentially activates autophagy in vascular smooth muscle cells
국내외구분 국외 SCI여부 SCI(E)
연구책임자역할 공저자
주저자명 Kim Y, Park JK
교신저자명 Kang SW
공동저자명 Kim Y, Park JK, Seo JH, Ryu HS, Lim KS, Jeong MH, Kang DH, Kang SW
게제년월일 2018-11-08
ISSN 2045-2322
Impact Factor 3.998
학술지명 Scientific Reports
서지사항 0집 / 8권 / 1호,   페이지(16551 - 16551)
요약초록문
(Abstract) 입력		 Although rapamycin is a well-known conformational inhibitor of mTORC1, it is now widely used for treating arterial restenosis. Various rapamycin analogues (rapalogue) have been made for applying to drug-eluting stents. Here we show that two major rapalogues, everolimus and biolimus, exert a differential effect on the mTORC1-mediated signaling pathways in vascular smooth muscle cells. In balloon-injured carotid arteries, both rapalogues strongly inhibit neointimal hyperplasia. Signaling pathway analyses reveal that everolimus exert cytotoxicity by increasing cellular reactive oxygen species and consequently reduce energy metabolism. By contrast, biolimus confers a preferential induction of autophagy by more strongly activating major autophagy regulator, ULK1, in vascular smooth muscle cells than everolimus does. As a consequence, the implantation of biolimus-eluting stent reduces endothelial loss, which in turn reduces inflammation, in porcine coronary arteries. Thus, this study reveals that a chemical derivatization can cause a change among mTORC1-dependent signaling pathways in vascular smooth muscle cells, thereby enabling to elicit a differential efficacy on arterial restenosis.
파일  B93.A_rapamycin_derivative_biolimus_preferentially_act.pdf (1.7M) DATE : 2021-05-21 11:37:39