Adenoviral-delivered angiopoietin-1 reduces the infarction and attenuates the progression of cardiac dysfunction in the rat model of acute myocardial infarction

Takahashi, Kazuhiro; Ito, Yoshinori; Morikawa, Masayuki; Kobune, Masayoshi; Huang, Jianhua; Tsukamoto, Masaru; Sasaki, Katsunori; Nakamura, Kiminori; Dehari, Hironari; Ikeda, K; Uchida, Hiroaki; Hirai, Sachie; Abe, Tomio; Hamada, Hirofumi

doi:10.1016/s1525-0016(03)00230-2

Cited by 71 publications

(69 citation statements)

References 46 publications

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“…Transplantation of hMSCs leads to a significantly improved function in the post-infarction left ventricle. Angiopoietin-1 has been shown to enhance angiogenesis and to attenuate progression of cardiac dysfunction after myocardial infarction [16,17]. In our study, the angiogenesis effect of Ang1 was not obvious.…”

Section: Discussioncontrasting

confidence: 57%

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

Shyu

Wang²,

Hung³

et al. 2005

J Biomed Sci

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SummaryBoth cell therapy and angiogenic growth factor gene therapy have been applied to animal studies and clinical trials. Little is known about the direct comparison between cell therapy and angiogenic growth factor gene therapy. The goal of this study was to compare the effects of human bone marrow-derived mesenchymal stem cells (hMSCs) transplantation and injection of angiogenic growth factor genes in a model of acute myocardial infarction in mice. The hMSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of hMSCs were identified by flow cytometry and immunophenotyping. Immediately after ligation of the left anterior descending coronary artery in male severe combined immunodeficient (SCID) mice, culture-expanded hMSCs or angiogenic growth factor genes were injected intramuscularly at the left anterior free wall. The engrafted hMSCs were positive for cardiac marker, desmin. Infarct size was significantly smaller in the hMSCs-treated group than in the angiopoietin-1 (Ang-1) or vascular endothelial growth factor (VEGF)-treated group at day 28 after infarction. hMSCs transplantation was better in decreasing left ventricular end-diastolic dimension and increasing fractional shortening than Ang1 or VEGF gene therapy. Capillary density was markedly increased after hMSCs transplantation than Ang1 and VEGF gene therapy. In conclusion, intramyocardial transplantation of hMSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium. hMSCs are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction. Transplantation of MSCs may become the future therapy for acute myocardial infarction for myocardial regeneration.

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Section: Discussioncontrasting

confidence: 57%

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

Shyu

Wang²,

Hung³

et al. 2005

J Biomed Sci

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show abstract

“…1,2 Nevertheless, newly formed vessels in the above studies were mainly capillaries whose efficacy in improving blood perfusion was inconclusive. For instance, Hershey et al 3 reported that newly formed vessels induced by VEGF were insufficient for the improving of collateral blood flow.…”

Section: Introductionmentioning

confidence: 99%

VEGF165 and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways

Zhou

Yang

et al. 2004

Gene Ther

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Angiogenic growth factors, vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) could decrease myocardial infarct size, which was assumed to be related with newly formed capillaries. We doubted that these capillaries could do this solely and the potential protective mechanisms of VEGF and Ang1 on myocardium need to be evaluated. Three types of adenoviruses encoding human VEGF 165 (Ad-VEGF 165 ), human angiopoietin-1 (Ad-Ang1) and green fluorescent protein (Ad-GFP, as a parallel control) were constructed. Experiments were taken both in vitro and in vivo. As in vitro, the antiapoptosis effect of VEGF 165 , Ang1 and VEGF 165 +Ang1 on cardiac myoblasts was observed, which seemed to be related with the activation of phosphatidylinositol-3 kinase and Bcl-2 pathways. As in vivo, adenoviruses were intramyocardially injected immediately after the ligation of the left anterior descending coronay arteries in rats. The results showed positive effect of VEGF 165 , Ang1 and VEGF 165 +Ang1 on decreasing the myocardial infarct size at the 7th day. Myocardial PI-3K activity and Bcl-2 expression were elevated relatively at the 3rd day. The protective effect of VEGF 165 and Ang1 on the myocardium may broaden their functional research and contribute to their clinical use in the future.

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“…ANG-1 has been reported to significantly increase arteriolar density and reduce infarct size leading to improved cardiac performance following AMI in rodent models [42,43]. Furthermore, ANG-1 has been suggested to enhance hemodynamics by forming more complex vascular network characterized by mature vessels of increased luminal size [44,45].…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin-1 promotes functional neovascularization that relieves ischemia by improving regional reperfusion in a swine chronic myocardial ischemia model

Shim

Zhang

et al. 2006

J Biomed Sci

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SummaryThis study investigates the long-term angiogenic effects of ANG-1 and VEGF in a swine chronic myocardial ischemia model. Four-weeks after gradual occlusion of the left circumflex coronary artery by ameroid constrictor, animals were injected with recombinant adenoviral vectors carrying either human ANG-1 (n=9), human VEGF 165 (n=10) or empty vector (n=7) into the left ventricle free wall supplied by the constricted artery. Left ventricular perfusion in animals that received AdANG-1 (3.25±0.16 ml/min/g, p<0.05) recovered robustly 4 weeks after gene transfer while ischemia persisted in the AdVEGF (1.09±0.13 ml/min/ g) and empty vector (1.20±0.03 ml/min/g) groups. Microvascular densities in the left ventricles of animals that received AdANG-1 (19.61±1.76/0.572 mm 2 myocardial tissue, p<0.05) and AdVEGF (18.17±1.43/ 0.572 mm 2 myocardial tissue, p<0.05) were significantly higher than animals that received empty vector (13.53±0.92/0.572 mm 2 myocardial tissue) 12 weeks after gene transfer. ANG-1, but not VEGF, contributed to enhanced regional perfusion by increasing arteriolar density (1.9±0.4/0.572 mm 2 myocardial tissue vs. 0.7±0.2/0.572 mm 2 myocardial tissue, p<0.05) of large-sized (50-100 lm) arterioles. These data demonstrate that gene transfer of ANG-1 and VEGF enhances angiogenesis, but ANG-1 promotes sustained improvement of ventricular perfusion that expedites recovery of ischemic myocardium via arteriogenesis.

show abstract

Adenoviral-delivered angiopoietin-1 reduces the infarction and attenuates the progression of cardiac dysfunction in the rat model of acute myocardial infarction

Cited by 71 publications

References 46 publications

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

VEGF165 and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways

Angiopoietin-1 promotes functional neovascularization that relieves ischemia by improving regional reperfusion in a swine chronic myocardial ischemia model

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