Cardiomyocyte hyperplasia after plasmid‐mediated vascular endothelial growth factor gene transfer in pigs with chronic myocardial ischemia

Laguens, Rubén M.; Meckert, Patricia Cabeza; Janavel, Gustavo Vera; Lorenzi, Andrea; Lascano, Elena C.; Negroni, Jorge A.; Valle, Héctor Del; Cuniberti, Luis; Martinez, V.; Dulbecco, Eduardo; Melo, Cynthia de Freitas; Fernández, Nahuel; Criscuolo, Marcelo; Crottogini, Alberto J.

doi:10.1002/jgm.478

Cited by 32 publications

(26 citation statements)

References 21 publications

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“…In addition to these two mechanisms, VEGF gene therapy has previously been shown to (1) promote arteriogenesis and (2) have a mitogenic effect on adult cardiomyocytes in large animal models of myocardial ischemia and infarction. [17][18][19] Both of these previously described mechanisms most likely also contribute to the significant decrease in myocardial infarct size seen in this study.…”

Section: Discussionsupporting

confidence: 58%

Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct

et al. 2008

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Section: Discussionsupporting

confidence: 58%

Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct

et al. 2008

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“…It has been previously reported in a canine model of ischemic cardiomiopathy, with myocardial perfusion analysis through scintillography, in which the gene encoding the green fluorescent protein was successfully transfected [21]. With a similar model, myocardial angiogenesis was induced by transmural injection of plasmodial VEGF 165 in MI areas of dogs [22].…”

Section: Myocardial Infarction Area and LV Remodelingmentioning

confidence: 97%

VEGF165 Gene Therapy Improves Left Ventricular Function and Exercise Capacity in Diabetic Rats after Myocardial Infarction: Impact on Mortality Rate

Rodrigues¹,

Mostarda²,

Rosa³

2012

J Diabetes Metab

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Despite the increased amount of evidence about the benefits of human vascular endothelial growth factors by plasmid (pHuVEGF 165 ) based gene transfer after an ischemic event, the effects of pHuVEGF 165 therapy in diabetic hearts after myocardial infarction (MI) remains poorly investigated. We evaluated the effects of intramyocardial pHuVEGF 165 injection on left ventricular (LV) morphometry, function and blood flow, maximal oxygen consumption (VO 2 max), and the total mortality rate of diabetic rats after MI. Male Wistar rats were divided into control (C), myocardial infarction+saline injection (I+SAL), myocardial infarction+pHuVEGF 165 injection (I+VEGF), diabetes+myocardial infarction+saline injection (DI+SAL), and diabetes+myocardial infarction+pHuVEGF 165 injection (DI+VEGF). MI was induced after 15 days of streptozotocin diabetes induction. One day after MI, the animals received pHuVEGF 165 or saline intramyocardial injection. LV function and maximal oxygen consumption (VO 2 max) were evaluated at the initial injection and 30 days after injections. MI area evaluation showed an additional reduction in DI+VEGF (8±1%) in comparison with group I+VEGF (31±3%). Improvement in systolic function, evaluated invasively and noninvasively, lung wet/dry weight ratio, and VO 2 max were observed in both pHuVEGF 165 injected groups. Consequently, mortality rate was reduced in I+VEGF (19%) and DI+VEGF (12.5%) when compared with I+SAL (48%) and DI+SAL (37.5%) groups. In conclusion, pHuVEGF 165 therapy resulted in reduced MI area, stabilization and maintenance of left ventricular function, increased VO 2 max, and reduced mortality in MI animals, diabetic or not. These results highlight the importance of continuing experimental studies and controlled clinical trials of gene therapy for ischemic cardiomiopathy associated with the pathological conditions of diabetes.

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“…VEGF 165 has been the most frequently tested growth factor in large animal gene transfer studies. 14,[42][43][44][45][46][47][48][49][50][51][52][53][54] This form enhances collateral formation and myocardial perfusion in ameroid constrictor chronic ischemia models 46,48,50,54 as well as in coronary artery ligation ischemia models. 14,51,52 VEGF 121 gene transfer was evaluated in the chronic ischemia model, 20,55 and the pacing induced heart failure model, 26 showing improved myocardial perfusion and preserved cardiac function.…”

Section: Angiogenesismentioning

confidence: 99%

Cardiac gene therapy in large animals: bridge from bench to bedside

et al. 2012

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Cardiomyocyte hyperplasia after plasmid‐mediated vascular endothelial growth factor gene transfer in pigs with chronic myocardial ischemia

Cited by 32 publications

References 21 publications

Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct

Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct

VEGF165 Gene Therapy Improves Left Ventricular Function and Exercise Capacity in Diabetic Rats after Myocardial Infarction: Impact on Mortality Rate

Cardiac gene therapy in large animals: bridge from bench to bedside

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