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Artemisinin inhibits tumour necrosis factor‐ α ‐induced vascular smooth muscle cell proliferation in vitro and attenuates balloon injury‐induced neointima formation in rats
Author(s) -
Cao Qian,
Jiang Yan,
Shi Jin,
Liu Xue,
Chen Jie,
Niu Tiesheng,
Li Xiaodong
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12375
Subject(s) - neointima , cell cycle , vascular smooth muscle , apoptosis , cyclin d1 , cell growth , tumor necrosis factor alpha , cell cycle checkpoint , cyclin a , microbiology and biotechnology , chemistry , biology , cancer research , immunology , medicine , endocrinology , biochemistry , restenosis , smooth muscle , stent
Summary The aim of this study was to evaluate the effect of artemisinin ( ART ) on rat vascular smooth muscle cell ( VSMC ) proliferation induced by tumour necrosis factor ( TNF )‐ α , cell cycle arrest, and apoptosis, and its effect on neointima formation after balloon injury of rat carotid artery. Primary rat VSMC were identified by immunofluorescence assay. The proliferation of VSMC induced by TNF ‐ α was significantly inhibited by ART treatment in a dose‐dependent manner. Treatment with 100‐ μ M ART significantly reduced the expression of proliferating cell nuclear antigen. In contrast, the same treatment arrested the cell cycle in G0/G1 phase. Western blot analysis showed that the cell cycle‐related proteins cyclin D1, cyclin E, cyclin‐dependent kinase 2, and cyclin‐dependent kinase 4 were downregulated by ART in TNF ‐ α ‐stimulated VSMC . For apoptosis induced by ART , cleaved caspase‐3/‐9 was detected, and the pro‐apoptotic protein Bcl‐2‐associated X protein was upregulated while the anti‐apoptotic protein Bcl‐2 was downregulated. The results suggest that ART can effectively inhibit the proliferation of VSMC induced by TNF ‐ α through the apoptotic induction pathway and cell cycle arrest. Also, balloon injury indicated that ART significantly inhibited neointima formation in the rat carotid arteries.