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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (Ml) heart
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Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (Ml) heart

机译：VEGF和血管生成素1的共表达促进血管生成，心肌细胞增殖减少猪心肌梗死（M1）心脏的凋亡

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摘要

VEGF and angiopoietin-1 (Ang1) are two major angiogenic factors being investigated for the treatment of myocardial infarction (Ml). Targeting VEGF and Ang1 expression in the ischemic myocardium can increase their local therapeutic effects and reduce possible adverse effects. Adeno-associated viral vectors (AAVs) expressing cardiac-specific and hypoxia-inducible VEGF [AAV-myosin light chain-2v (MLC)VEGF] and Ang1 (AAV-MLCAng1) were coinjected (VEGF/Ang1 group) into six different sites of the porcine myocardium at the peri-infarct zone immediately after ligating the left descending coronary artery. An identical dose of AAV-Cytomegalovirus (CMV)LacZ or saline was injected into control animals. AAV genomes were detected in the liver in addition to the heart. RT-PCR, Western blotting, and ELISA analyses showed that VEGF and Ang1 were predominantly expressed in the myocardium in the infarct core and border of the infarct heart. Gated single-photon emission computed tomography analyses showed that the VEGF/Ang1 group had better cardiac function and myocardial perfusion at 8 wk than at 2 wk after vector injection. Compared with the saline and LacZ controls, the VEGF/Ang1 group expressed higher phosphorylated Akt and Bcl-xL, less Caspase-3 and Bad, and had higher vascular density, more proliferating cardiomyocytes, and less apoptotic cells in the infarct and peri-infarct zones. Thus, cardiac-specific and hypoxia-induced coexpression of VEGF and Ang1 improves the perfusion and function of porcine Ml heart through the induction of angiogenesis and cardiomyocyte proliferation, activation of prosurvival pathways, and reduction of cell apoptosis.
机译：VEGF和血管生成素-1（Ang1）是正在研究用于治疗心肌梗塞（M1）的两个主要血管生成因子。靶向缺血心肌中的VEGF和Ang1表达可以增加其局部治疗作用并减少可能的不良反应。将表达心脏特异性和低氧诱导性VEGF [AAV-肌球蛋白轻链2v（MLC）VEGF]和Ang1（AAV-MLCAng1）的腺相关病毒载体（AAV）共注入（VEGF / Ang1组）的六个不同部位结扎左冠状动脉下降后立即在梗死区周围的猪心肌。将相同剂量的AAV巨细胞病毒（CMV）LacZ或盐水注入对照动物。除心脏外，还在肝脏中检测到AAV基因组。 RT-PCR，Western印迹和ELISA分析表明，VEGF和Ang1主要在梗塞心脏和梗塞心脏边界的心肌中表达。门控单光子发射计算机断层扫描分析显示，在注射载体后8周时，VEGF / Ang1组的心脏功能和心肌灌注优于2周时。与生理盐水和LacZ对照相比，VEGF / Ang1组在梗死灶和梗死灶周围表达更高的磷酸化Akt和Bcl-xL，更少的Caspase-3和Bad，并且具有更高的血管密度，更多的心肌细胞增殖和更少的凋亡细胞。区域。因此，心脏特异性和低氧诱导的VEGF和Ang1的共表达通过诱导血管生成和心肌细胞增殖，激活存活途径和减少细胞凋亡来改善猪M1心脏的灌注和功能。

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  • 作者

    Zhengxian Tao; Bo Chen; Xiao Tan; Yingming Zhao; Liansheng Wang; Tiebing Zhu; Kejiang Cao; Zhijian Yang; Yuet Wai Kan; Hua Su;

  • 作者单位

    Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China;

    Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China;

    Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China;

    Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China;

    Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China;

    Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China;

    Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China;

    Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China;

    Department of Medicine, University of California, San Francisco, CA 94143-0793;

    Center for Cerebrovascular Research, Department of Anesthesia and Perioperative, University of California, San Francisco, CA 94143-0793;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    coronary disease; gene therapy;

    机译：冠心病;基因治疗;

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