A rapamycin derivative, biolimus, preferentially activates autophagy in vascular smooth muscle cells
- 주제(기타) Multidisciplinary Sciences
- 설명문(일반) [Kim, Yerin; Kang, Dong Hoon; Kang, Sang Won] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Kang, Sang Won] Vasthera Co Ltd, Seoul 03760, South Korea; [Park, Jun Kyu; Seo, Jun-Hyuk; Ryu, Hyun-Seung] CGBio Ltd, Jangseong 57248, South Korea; [Lim, Kyung Seob; Jeong, Myung Ho] Chonnam Natl Univ, Cardiovasc Res Ctr, Gwangju 61469, South Korea; [Kang, Dong Hoon] Univ Ulsan, Coll Med, Dept Asan Inst Life Sci, Asan Med Ctr, Seoul 05505, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000155948
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s41598-018-34877-8
초록/요약
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.
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