DHEA inhibits vascular remodeling following arterial injury: a possible role in suppression of inflammation and oxidative stress derived from vascular smooth muscle cells

• Published in: Molecular and cellular biochemistry Vol. 388; no. 1-2; pp. 75 - 84
• Main Authors: Chen, Jiangbin, Xu, Lin, Huang, Congxin
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2014; Springer; Springer Nature B.V
• Subjects: Analysis; Androgens; Angiotensin II - biosynthesis; Animals; Aorta, Thoracic - injuries; Aorta, Thoracic - pathology; Biochemistry; Biomedical and Life Sciences; Cardiology; Carotid Artery Injuries - drug therapy; Carotid Artery Injuries - pathology; Cell Movement; Cell Proliferation - drug effects; Cells; Cells, Cultured; Dehydroepiandrosterone; Dehydroepiandrosterone - pharmacology; Dinoprost - blood; Enzyme-linked immunosorbent assay; Extracellular Signal-Regulated MAP Kinases - metabolism; Fluorescence; Inflammation; Inflammation - drug therapy; Inflammatory diseases; Life Sciences; Male; MAP Kinase Signaling System - drug effects; Medical Biochemistry; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - pathology; Muscular system; NADP - metabolism; NADPH Oxidases - biosynthesis; Neointima - metabolism; Neointima - pathology; Oncology; Oxidases; Oxidative stress; Oxidative Stress - drug effects; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; Phosphorylation - drug effects; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Regeneration - drug effects; Smooth muscle; Superoxide Dismutase - biosynthesis; Transcription Factor RelA - antagonists & inhibitors; Transcription Factor RelA - biosynthesis; Vascular System Injuries - drug therapy; Vascular System Injuries - pathology; Veins & arteries; Oxidative stress; Dehydroepiandrosterone; Inflammation; Carotid artery balloon injury; Vascular smooth muscle cells
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-013-1900-7

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.