title: [Effect of gene modified mesenchymal stem cells overexpression human receptor activity modified protein 1 on inflammation and cardiac repair in a rabbit model of myocardial infarction].
abstract: OBJECTIVE
  To investigate the effect of mesenchymal stem cells (MSCs) overexpressing human receptor activity modified protein 1 (hRAMP1) by adenovirus vector on infarction related inflammation and cardiac repair in a rabbit model of myocardial infarction (MI).
  
  
  METHODS
  Thirty rabbits underwent coronary artery ligation for 60 minutes followed by 24 hours reperfusion and divided into MSC(hRAMP1) group (intravenously injection of MSCs transfected with adenovirus vector encoding hRAMP1 gene enhanced green fluorescent protein, EGFP, n = 10), MSC(null) group (MSCs transfected with adenovirus vector encoding only EGFP without hRAMP1 gene, n = 10) and control group (equally volume of phosphate buffered saline, PBS, n = 10). The plasma level of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were quantified by ELISA assay at before and 1, 3, 7, 28 days after induction of MI. The expression of nuclear factor-κB (NF-κB) and hRAMP1 in infracted myocardium were measured by Western blot at 1, 3, 7, 28 day following MI. The area of MI and collagen deposition and fibrosis were evaluated by TTC staining and Masson staining, respectively.
  
  
  RESULTS
  Area of MI and collagen content were significantly reduced in MSC(hRAMP1) group compared those in MSC(null) and control group [(10.1 ± 2.9)% vs. (30.6 ± 2.7)% and (22.5 ± 3.2)%, P < 0.05]. Myocardial expression of NF-κB and plasma TNF-α[7 days after transplantation: (97.2 ± 6.7) pg/ml vs. (207.6 ± 12.7) pg/ml and (153.2 ± 9.9) pg/ml, P < 0.05] were also lower while plasma level of IL-10 [7 days after transplantation: (238.5 ± 17.5) pg/ml vs. (177.3 ± 19.8) pg/ml and (244.6 ± 27.3) pg/ml, P < 0.05] was significantly higher in MSC(hRAMP1) group than in MSC(null) and control group.
  
  
  CONCLUSIONS
  MSCs overexpression hRAMP1 could further reduce area of MI possibly through inhibiting the myocardial expression of NF-κB and reducing the plasma TNF-α level and raising plasma IL-10 level.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Zunyi Medical College, Zunyi, China.
authors.forename: Ran-zun
authors.initials: RZ
authors.lastname: Zhao
authors.forename: Xian-ping
authors.initials: XP
authors.lastname: Long
authors.forename: Zhi-jiang
authors.initials: ZJ
authors.lastname: Liu
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Wang
authors.forename: Bei
authors.initials: B
authors.lastname: Shi
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D005822:Genetic Vectors; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D058262:Receptor Activity-Modifying Protein 1 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D058262:Receptor Activity-Modifying Protein 1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10