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DHEA inhibits vascular remodeling following arterial injury: a possible role in suppression of inflammation and oxidative stress derived from vascular smooth muscle cells.
- Source :
-
Molecular and cellular biochemistry [Mol Cell Biochem] 2014 Mar; Vol. 388 (1-2), pp. 75-84. Date of Electronic Publication: 2013 Nov 28. - Publication Year :
- 2014
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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.
- Subjects :
- Angiotensin II biosynthesis
Animals
Aorta, Thoracic pathology
Carotid Artery Injuries pathology
Cell Movement
Cell Proliferation drug effects
Cells, Cultured
Dinoprost blood
Extracellular Signal-Regulated MAP Kinases metabolism
Inflammation drug therapy
MAP Kinase Signaling System drug effects
Male
Muscle, Smooth, Vascular cytology
NADP metabolism
NADPH Oxidases biosynthesis
Neointima metabolism
Neointima pathology
Oxidative Stress drug effects
Phosphorylation drug effects
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species metabolism
Regeneration drug effects
Superoxide Dismutase biosynthesis
Transcription Factor RelA antagonists & inhibitors
Transcription Factor RelA biosynthesis
Vascular System Injuries pathology
p38 Mitogen-Activated Protein Kinases antagonists & inhibitors
Aorta, Thoracic injuries
Carotid Artery Injuries drug therapy
Dehydroepiandrosterone pharmacology
Muscle, Smooth, Vascular pathology
Vascular System Injuries drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4919
- Volume :
- 388
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 24287563
- Full Text :
- https://doi.org/10.1007/s11010-013-1900-7