title: [Effects of recombinant human erythropoietin on angiogenesis in chronic ischemic porcine myocardium].
abstract: OBJECTIVE
  To investigate the effect and mechanism of recombinant human erythropoietin (rhEPO) on angiogenesis in chronic ischemic porcine myocardium.
  
  
  METHODS
  A ameroid constrictor was placed around the proximal circumflex branch of the left coronary artery in 12 Bama miniatures' swine artery by thoracoscopy. Electrocardiogram and coronary angiography were used to confirm the establishment of myocardial ischemia. The animals were divided into rhEPO treatment group (n = 6) and negative control group (n = 6). Treatment group received subcutaneous injection of rhEPO at 1, 3, 7, 14, 21 days, control group received saline. The expression of vascular endothelial growth factor (VEGF) in serum was assessed by ELISA. Ultrasonography and coronary angiography were assessed 28 days after therapy. Western blot was used to detect the expression of VEGF, phosphorylated protein kinase B (p-Akt) and phosphorylated extracellular signal regulated kinases (p-Erk). The degree of angiogenesis was assessed by immunohistochemical analysis.
  
  
  RESULTS
  Serum VEGF rose significantly in both control and treatment groups, peaking at 3 days and then returning to the near-baseline level at 28 days, but the two groups showed no significant difference at each time point (P > 0.05). Echocardiographic measurements showed that the left ventricular systolic function of animals in treatment group increase significantly after rhEPO therapy. the expression levels of VEGF, p-Akt and p-Erk had markedly increased, which resulted in a 2.5-fold increased of VEGF, 1.1-fold increased of p-Akt, 1.5-fold increased of p-Erk (t = 37.721, 10.907, 12.957, all P = 0.000). there were significant increase in capillary density and arteriole density in the two groups ((944 ± 98) %/mm² vs. (569 ± 102) %/mm², (73 ± 13) %/mm² vs. (45 ± 10) %/mm², t = 4.214, 2.869, P = 0.016, 0.023).
  
  
  CONCLUSIONS
  rhEPO can promote angiogenesis and arteriogenesis and improve the left ventricular systolic function in porcine model of chronic myocardial ischemia. The potential mechanism is to up-regulated the expression of p-Akt and p-Erk.
authors.affiliation: Department of Thoracic Surgery, Taizhou Hospital, Linhai 317000, Zhejiang Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Lilong
authors.initials: L
authors.lastname: Xia
authors.forename: Bingchuan
authors.initials: B
authors.lastname: Hu
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Email: zhucc669266@163.com.
authors.forename: Chengchu
authors.initials: C
authors.lastname: Zhu
authors.forename: Baofu
authors.initials: B
authors.lastname: Chen
authors.forename: Yibing
authors.initials: Y
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D000068817:Epoetin Alfa; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases