title: IL-8 up-regulates proliferative angiogenesis in ischemic myocardium in rabbits through phosphorylation of Akt/GSK-3β(ser9) dependent pathways.
abstract: BACKGROUND
  Therapeutic myocardial angiogenesis is an important compensatory mechanism in severely coronary stenosis. Previous studies demonstrated that interleukin-8 (IL-8) not only plays an important role in inflammation, but also a potent angiogenic factor through p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-kappaB (NK-κB)-dependent pathway in carcinoma. Our study sought to investigate the effects of IL-8 on the angiogenesis and the underlying mechanism in the ischemic myocardium.
  
  
  METHODS
  Acute myocardial infarction animal model was established with male rabbits by directly suturing the left anterior descending branch, then lentivirus-mediated IL-8 was quarterly injected into the borderline of infarction area immediately. We employed CoCl2 induced hypoxic HUVECs for in vitro ischemia study. Left ventricular end-diastolic diameter (LVEDd) and ejection fraction (EF) were measured by echocardiography in pre-operation and at 6(th) week after operation. CD34 was detected with immunohistochemisty to analyse angiogenesis. Western blot was performed with regard to IL-8, protein kinase B (PKB/Akt) and Glycogen synthase kinase-3β(ser9) (GSK-3β(ser9)). For the HUVECs' proliferation and apoptosis, multiscan spectrum reader at A570 nm and annexin V-FITC/PI staining method were used respectively.
  
  
  RESULTS
  The levels of IL-8, phosphorylated Akt and GSK-3β(ser9) in focal myocardium significantly increased, and the over expression of IL-8 led to an increasing in angiogenesis in rabbits. Hypoxia inhibited cell proliferation and promoted apoptosis. IL-8 induced cell proliferation, phosphorylation of Akt and GSK-3β(ser9), inhibited apoptosis and Caspase3 expression in HUVECs, which were attenuated by anti-IL-8 or the Akt inhibitor LY294002.
  
  
  CONCLUSIONS
  The present results indicate that IL-8 can increase angiogenesis in myocardial infarction, which maybe through enhancing Akt and GSK-3β(ser9) expression, and inhibiting myocardial apoptosis.
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University Changsha 410008, P. R. China.
authors.forename: Qiying
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University Changsha 410008, P. R. China.
authors.forename: Zelin
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University Changsha 410008, P. R. China.
authors.forename: Meifang
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The 1st People's Hospital of Chenzhou City Chenzhou 423000, P. R. China.
authors.forename: Qiaoqing
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University Changsha 410008, P. R. China.
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University Changsha 410008, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yi
keywords: Akt/GSK-3βser9 pathways; IL-8; angiogenesis; ischemic myocardium