Cilostazol inhibits high glucose- and angiotensin II-induced type 1 plasminogen activator inhibitor expression in artery wall and neointimal region after vascular injury

Authors
Kyeong-Min LeeHyo-Jeong LeeMi-Kyung KimHye-Soon KimGwon-Soo JungSeung-Ho HurHyoung Tae KimWon-Hyun ChoJung-Guk KimBo-Wan KimJeong Ok LimHueng-Sik ChoiKi-Up LeeKeun-Gyu ParkIn-Kyu Lee
Department
Dept. of Internal Medicine (내과학); Dept. of Surgery (외과학)
Issue Date
2009
Citation
Atherosclerosis, Vol.207(2) : 391-398, 2009
ISSN
0021-9150
Abstract
Increased expression of plasminogen activator inhibitor-1 (PAI-1) in vascular tissues is a potential factor linking diabetes to restenosis after percutaneous coronary intervention. Recent studies have shown that cilostazol, a selective type 3 phosphodiesterase inhibitor, prevents neointimal hyperplasia and instent thrombosis in patients with diabetes after coronary angioplasty and stent implantation. However, the molecular mechanism of this drug has not been fully elucidated. We examined whether cilostazol inhibits PAI-1 expression in vascular smooth muscle cells (VSMCs) and neointimal hyperplasia.We found that cilostazol effectively inhibits angiotensin II-, high glucose- and TGF- -stimulated PAI-1 expression in vivo and in vitro. Cilostazol attenuated PAI-1 expression in neointimal regions and inhibited neointimal hyperplasia after balloon injury. Cilostazol inhibited PAI-1 expression by multiple mechanisms including downregulation of TGF- , JNK and p38 signaling pathways. Cilostazol also inhibited transactivating activity at the PAI-1 promoter by Smad3, leading to a suppression of PAI-1 gene transcription. Taken together with its antiproliferative effect on VSMCs, this may explain how cilostazol exerts its antithrombogenic effects after angioplasty and stent implantation.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35135
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
Keimyung Author(s)
김미경; 김혜순; 허승호; 박근규; 김형태; 조원현
Full Text
https://www.sciencedirect.com/science/article/pii/S0021915009004857?via%3Dihub
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