title: Phenotypic switching of vascular smooth muscle cells in animal model of rat thoracic aortic aneurysm.
abstract: OBJECTIVE
  To explore if there is phenotypic switching in the vascular smooth muscle cells (vSMCs) of rat thoracic aortic aneurysms and the role it plays in the process of aneurysm formation.
  
  
  METHODS
  Male SD white rats were assigned randomly to the aneurysm group (AG) and control group (CG). The animal aneurysm model was obtained by soaking the peri-adventitia with porcine pancreatic elastase (PPE). The rats in the CG were given saline to provide contrast. A vascular ultrasound was used to monitor the diameter of the aneurysm. Specimens were stained with haematoxylin and eosin (HE), and α-SMA, SM-MHC, matrix metalloproteinase (MMP)-2 and MMP-9 were detected with immunohistochemistry staining. α-SMA, SM-MHC, MMP-2 and MMP-9 were conducted with western blot. vSMCs taken from the descending aorta of both of the CG and AG were separated and cultured until Passage 3. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method were used to analyse cell proliferation. Western blot was used to evaluate MMP-2, MMP-9 expression and flow cytometry was employed to assess cell apoptosis.
  
  
  RESULTS
  Vascular ultrasound showed obvious dilatation of soaked descending aorta. HE staining showed thickening of thoracic aorta and disarrangement of cells after soaking with PPE. Immunohistochemistry staining showed high expression of MMP-2 and MMP-9 but low expression of SM-MHC and α-SMA in the AG. Tissue western blot analysis of the AG showed that the protein gray value was high in MMP-2 and MMP-9, but low in α-SMA and SM-MHC, which had statistical differences compared with CG with a P-value of <0.05. MTT analysis showed vSMC proliferation activity was higher in the AG than in the CG. Flow cytometry analysis revealed that cell apoptosis between the control and aneurysm groups had significant statistical differences.
  
  
  CONCLUSIONS
  There is vSMC phenotypic switching in animal models as seen through the rat thoracic aortic aneurysms. This may play an important role in the formation of aneurysms. Our findings are relevant to human aneurysms and may be conducive in the research of aortic aneurysm pathology and treatment.
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Naihui
authors.initials: N
authors.lastname: Mao
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China maonaihuihans@126.com.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Gu
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Enyi
authors.initials: E
authors.lastname: Shi
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging / Q000378:metabolism; D017545:Aortic Aneurysm, Thoracic / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D010196:Pancreatic Elastase; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D018615:Ultrasonography, Doppler, Color
chemical_list: D000199:Actins; D015415:Biomarkers; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D018995:Myosin Heavy Chains; D010196:Pancreatic Elastase; C000595077:Myh11 protein, rat; C498862:Acta2 protein, rat; C522363:Mmp2 protein, rat; C572337:Mmp9 protein, rat
keywords: Phenotype switch; Thoracic aortic aneurysm; Vascular smooth muscle cell