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Anti-malarial Drugs Reduce Vascular Smooth Muscle Cell Proliferation via Activation of AMPK and Inhibition of Smad3 Signaling
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Anti-malarial Drugs Reduce Vascular Smooth Muscle Cell Proliferation via Activation of AMPK and Inhibition of Smad3 Signaling

논문 기본 정보

자료유형
학술저널
저자정보
저널정보
한국지질동맥경화학회(구 한국지질학회) 지질·동맥경화학회지 지질·동맥경화학회지 제8권 제2호 KCI Accredited Journals
발행연도
2019.1
수록면
267 - 276 (10page)

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Anti-malarial Drugs Reduce Vascular Smooth Muscle Cell Proliferation via Activation of AMPK and Inhibition of Smad3 Signaling
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Objective The aim of this study was to investigate the effects of 2 anti-malarial drugs, chloroquine (CQ) and hydroxychloroquine (HCQ), on inhibition of vascular smooth muscle cell (VSMC) proliferation both in vivo and in vitro via Adenosine monophosphate-activated protein kinase (AMPK) activation. Methods Protein and mRNA levels were determined by western blot analysis and real-time reverse transcription-polymerase chain reaction in primary rat VSMCs treated with CQ and HCQ, respectively. Cell proliferation was measured by flow cytometry and cell counting. Mice carotid arteries were ligated and treated with CQ or HCQ every other day for 3 weeks. Pathological changes of carotid arteries were visualized by both microscopy and fluorescence microscopy. Results CQ and HCQ increase AMPK phosphorylation in VSMCs. Both CQ and HCQ decrease platelet-derived growth factor-induced VSMC proliferation and cell cycle progression in an AMPK-dependent manner. In addition, CQ and HCQ inhibit Smad3 phosphorylation and VSMC proliferation induced by transforming growth factor-β1. Moreover, CQ and HCQ diminished neointimal proliferation in a mouse model of carotid artery ligation-induced neointima formation. Conclusion The results demonstrated that CQ and HCQ inhibit cell proliferation and cell cycle progression in VSMCs via the AMPK-dependent signaling pathway. Carotid artery ligation-induced intima thickness was reduced in mouse arteries treated with CQ or HCQ, suggesting a role for antimalarial drugs in treating atherosclerosis and restenosis.

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