title: Artemisinin inhibits tumour necrosis factor-α-induced vascular smooth muscle cell proliferation in vitro and attenuates balloon injury-induced neointima formation in rats.
abstract: 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-μM 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.
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Jin
authors.initials: J
authors.lastname: Shi
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Tiesheng
authors.initials: T
authors.lastname: Niu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000293:injuries* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology*; D058426:Neointima / Q000188:drug therapy* / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D037621:Artemisinins; D014409:Tumor Necrosis Factor-alpha; C031327:artemisinin
keywords: TNF-α; apoptosis; artemisinin; cell cycle; neointima formation; proliferation; vascular smooth muscle cells