Combination of angiopoietin-1 and vascular endothelial growth factor gene therapy enhances arteriogenesis in the ischemic myocardium

Siddiqui, Anwar J.; Blomberg, Pontus; Wärdell, Eva; Hellgren, Irina; Eskandarpour, Malihe; Islam, Khalid B.; Sylvén, Christer

doi:10.1016/j.bbrc.2003.09.111

Cited by 73 publications

(48 citation statements)

References 23 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: 59%

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: 59%

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

“…Expression of ang-1 did increase the number of α-SMA positive vessels; however, co-expression of ang-1 with VEGF did not increase the vessel density above the levels of VEGF. This result is somewhat different from that of Siddiqui et al, where they transiently expressed VEGF and ang-1 in normal and ischemic mouse hearts by plasmidmediated gene transfer (18). They showed that ang-1 alone could increase CAP density in both normal and ischemic mouse hearts.…”

Section: Discussioncontrasting

confidence: 81%

“…Although co-expression of VEGF and ang-1 in ischemic hindlimb and heart has been proven to induce leakage resistant vessels and resulted in some improvements in angiogenesis and therapy (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Most of the experiments used plasmid as the vector, which only results in short-term gene expression.…”

Section: Discussionmentioning

confidence: 99%

Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart

Takagawa

Huang

et al. 2009

International Journal of Cardiology

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Vascular endothelial growth factor (VEGF) is a key angiogenic factor and has been used experimentally for induction of neovasculature in ischemic myocardium. However, blood vessels induced by VEGF are immature. Angiopoietin-1 (ang-1) has the ability to recruit and sustain periendothelial support cells and promote vascular maturation. Thus, co-expression of the two may yield a better result than expression of either one alone. Two adeno-associated viral vectors (AAV), CMVVEGF and CMVang-1 with the CMV promoter driving VEGF or ang-1 gene expression, respectively, were injected into ischemic mouse hearts individually or together in different ratios. The results show that co-injected groups had more capillaries than the CMVang-1 group and similar densities of capillaries and α-actin positive vessels as the CMVVEGF group. Neovasculature induced by CMVVEGF was leaky. In contrast, neovasculature in CMVang-1-injected or CMVVEGF and CMVang-1 co-injected hearts was less leaky than that in CMVVEGF-injected hearts. The group that received CMVang-1 and CMVVEGF in a 1:1 ratio had the smallest infarct size and best cardiac function and regional wall movement among all the groups. We conclude that ang-1 and VEGF can compensate for each others' shortcomings and yield a better therapeutic effect by acting together.

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“…It should be noted that improvement of cardiac dysfunction after MI has been successfully achieved by gene therapy using angiogenic factors that do not directly act on cardiomyocytes. 29,43 This fact suggests that angiogenesis plays a crucial role in postinfarction remodeling, and that the absence of an angiogenic effect of overexpressed HB-EGF may be largely responsible for its lack of therapeutic action.…”

Section: Discussionmentioning

confidence: 99%

Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes

Ushikoshi

Takahashi

Chen

et al. 2005

Laboratory Investigation

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Insulin-like growth factor (IGF), hepatocyte growth factor (HGF), and heparin-binding epidermal growth factorlike growth factor (HB-EGF) are cardiogenic and cardiohypertrophic growth factors. Although the therapeutic effects of IGF and HGF have been well demonstrated in injured hearts, it is uncertain whether natural upregulation of HB-EGF after myocardial infarction (MI) plays a beneficial or pathological role in the process of remodeling. To answer this question, we conducted adenoviral HB-EGF gene transduction in in vitro and in vivo injured heart models, allowing us to highlight and explore the HB-EGF-induced phenotypes. Overexpressed HB-EGF had no cytoprotective or additive death-inducible effect on Fas-induced apoptosis or oxidative stress injury in primary cultured mouse cardiomyocytes, although it significantly induced hypertrophy of cardiomyocytes and proliferation of cardiac fibroblasts. Locally overexpressed HB-EGF in the MI border area in rabbit hearts did not improve cardiac function or exhibit an angiogenic effect, and instead exacerbated remodeling at the subacute and chronic stages post-MI. Namely, it elevated the levels of apoptosis, fibrosis, and the accumulation of myofibroblasts and macrophages in the MI area, in addition to inducing left ventricular hypertrophy. Thus, upregulated HB-EGF plays a pathophysiological role in injured hearts in contrast to the therapeutic roles of IGF and HGF. These results imply that regulation of HB-EGF may be a therapeutic target for treating cardiac hypertrophy and fibrosis. Laboratory Investigation (2005) 85, 862-873.

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Combination of angiopoietin-1 and vascular endothelial growth factor gene therapy enhances arteriogenesis in the ischemic myocardium

Cited by 73 publications

References 23 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

Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart

Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes

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