title: Lithium chloride inhibits vascular smooth muscle cell proliferation and migration and alleviates injury-induced neointimal hyperplasia via induction of PGC-1α.
abstract: The proliferation and migration of vascular smooth muscle cells (VSMCs) contributes importantly to the development of in-stent restenosis. Lithium has recently been shown to have beneficial effects on the cardiovascular system, but its actions in VSMCs and the direct molecular target responsible for its action remains unknown. On the other hand, PGC-1α is a transcriptional coactivator which negatively regulates the pathological activation of VSMCs. Therefore, the purpose of the present study is to determine if lithium chloride (LiCl) retards VSMC proliferation and migration and if PGC-1α mediates the effects of lithium on VSMCs. We found that pretreatment of LiCl increased PGC-1α protein expression and nuclear translocation in a dose-dependent manner. MTT and EdU incorporation assays indicated that LiCl inhibited serum-induced VSMC proliferation. Similarly, deceleration of VSMC migration was confirmed by wound healing and transwell assays. LiCl also suppressed ROS generation and cell cycle progression. At the molecular level, LiCl reduced the protein expression levels or phosphorylation of key regulators involved in the cell cycle re-entry, adhesion, inflammation and motility. In addition, in vivo administration of LiCl alleviated the pathophysiological changes in balloon injury-induced neointima hyperplasia. More importantly, knockdown of PGC-1α by siRNA significantly attenuated the beneficial effects of LiCl on VSMCs both in vitro and in vivo. Taken together, our results suggest that LiCl has great potentials in the prevention and treatment of cardiovascular diseases related to VSMC abnormal proliferation and migration. In addition, PGC-1α may serve as a promising drug target to regulate cardiovascular physiological homeostasis.
authors: Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China.
authors: Zhuyao
authors: Z
authors: Wang
authors: Xiwen
authors: X
authors: Zhang
authors: Siyu
authors: S
authors: Chen
authors: Danfeng
authors: D
authors: Wang
authors: Jun
authors: J
authors: Wu
authors: Tingming
authors: T
authors: Liang
authors: Chang
authors: C
authors: Liu
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006965:Hyperplasia; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D058426:Neointima / Q000378:metabolism* / Q000473:pathology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D042442:Vascular Endothelial Growth Factors; D018021:Lithium Chloride
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