title: Resveratrol inhibits phenotypic switching of neointimal vascular smooth muscle cells after balloon injury through blockade of Notch pathway.
abstract: BACKGROUND
  Phenotypic switching of vascular smooth muscle cells (VSMCs) plays an initial role in neointimal hyperplasia, the main cause of many occlusive vascular diseases. The aim of this study was to measure the effects of resveratrol (RSV) on the phenotypic transformation of VSMCs and to investigate its mechanism of action.
  
  
  METHODS
  Cultured VSMCs isolated from rat thoracic aorta were prepared with serum starvation for 72 hours followed by RSV treatment (50-200 μmol/L) and 10% serum stimulation. Male Sprague-Dawley rats, subjected to carotid arteries injury from a balloon catheter, were exposed to intraperitoneal injection of RSV (1 mg/kg) or saline and were killed after 7 or 28 days.
  
  
  RESULTS
  Compared with cells in the serum-induced group, VSMCs in the RSV or N-[N-(3, 5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) treatment group exhibited significant decreases of proliferation and migration. The total and cytoplasmic Notch-1 levels were declined by RSV, accompanied by a significant increase in smooth muscle α-actin and smooth muscle myosin heavy chain protein. The expression of Notch-1, Jagged-1, Hey-1, and Hey-2 mRNA in balloon-injured arteries at 7 days was decreased by RSV treatment. Arteries from RSV-treated rats showed less neointimal hyperplasia, lower collagen content, and a lower rate of cells positive for proliferating cell nuclear antigen 28 days after injury, compared with saline controls.
  
  
  CONCLUSIONS
  The results indicate that RSV can attenuate phenotypic switching of VSMCs after arterial injury through inhibition of the Notch pathway.
authors.affiliation: *Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; †Departments of Cardiology; and ‡Ophthalmology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Changwu
authors.initials: C
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.forename: Qi
authors.initials: Q
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D058426:Neointima / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000235:genetics*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000975:Antioxidants; C497763:Notch1 protein, rat; D051881:Receptor, Notch1; D013267:Stilbenes; D000077185:Resveratrol