Cilostazol inhibits high glucose- and angiotensin II-induced type 1 plasminogen activator inhibitor expression in artery wall and neointimal region after vascular injury
- Affiliated Author(s)
- 김미경; 김혜순; 허승호; 박근규; 김형태; 조원현
- Alternative Author(s)
- Kim, Mi Kyung; Kim, Hye Soon; Hur, Seung Ho; Park, Keun Gyu; Kim, Hyoung Tae; Cho, Won Hyun
- Journal Title
- Atherosclerosis
- ISSN
- 0021-9150
- Issued Date
- 2009
- 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.
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