title: DHEA inhibits vascular remodeling following arterial injury: a possible role in suppression of inflammation and oxidative stress derived from vascular smooth muscle cells.
abstract: Vascular remodeling is characterized by the aggregation of vascular smooth muscle cells (VSMCs) in intima. Previous studies have demonstrated that dehydroepiandrosterone (DHEA), a steroid hormone, can reverse vascular remodeling. However, it is still far clear that whether and how DHEA participates in the modulation of VSMCs activation and vascular remodeling. VSMCs were obtained from the thoracic aorta of SD rats. Cell proliferation was evaluated by CCK-8 assay and BrdU assay. To measure VSMCs migration activity, a transwell chamber assay was performed. Quantitative real-time RT-PCR and western blot were used to explore the molecular mechanisms. ROS generation by VSMCs was measured by DCF fluorescence. NADPH oxidase activity and SOD activity were measured by the corresponding kits. NF-κB activity was detected by NF-κB luciferase reporter gene assay. A rat carotid artery balloon injury model was built to evaluate the neointimal formation, and plasma PGF2 was measured by ELISA. Our results showed that DHEA significantly inhibited VSMCs proliferation after angiotensin (Ang II) stimulation by down-regulation of NADPH oxidase activity and ERK1/2 phosphorylation. Ang II can increase IL-6 and MCP-1 expression, but DHEA reverses these changes via inhibiting p38-MAPK/NF-κB (p65) signaling pathway. DHEA has no significant effects on VSMCs phenotype transition, but can reduce the neointimal to media area ratio after balloon injury. DHEA can alleviate oxidative stress and inflammation in VSMCs via ERK1/2 and NF-κB signaling pathway, but has no effect on VSMCs phenotype transition. Furthermore, DHEA attenuates VSMCs activation and neointimal formation after carotid injury in vivo. Taken together, DHEA might be a promising treatment for vascular injury under pathological condition.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
authors.forename: Jiangbin
authors.initials: J
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D000804:Angiotensin II / Q000096:biosynthesis; D000818:Animals; D001013:Aorta, Thoracic / Q000293:injuries* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D015237:Dinoprost / Q000097:blood; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000473:pathology*; D009249:NADP / Q000378:metabolism; D019255:NADPH Oxidases / Q000096:biosynthesis; D058426:Neointima / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D013482:Superoxide Dismutase / Q000096:biosynthesis; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D057772:Vascular System Injuries / Q000188:drug therapy* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: C498143:RELA protein, human; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D000804:Angiotensin II; D003687:Dehydroepiandrosterone; D009249:NADP; D015237:Dinoprost; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases