VEGF(165) Gene Therapy Improves Left Ventricular Function and Exercise Capacity in Diabetic Rats after Myocardial Infarction: Impact on Mortality Rate

Author(s)

Rodrigues, Bruno ; Mostarda, Cristiano T. ; Rosa, Kaleizu T. ; Markoski, Melissa ; Nardi, Nance B. ; De Angelis, Katia ; Irigoyen, Maria Claudia ; Kalil, Renato A. K.

• Document type: Journal article
• Source: JOURNAL OF DIABETES & METABOLISM; v. 3, p. 8-pg., 2012-01-01.

Abstract

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 (VO2 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 (VO2 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 VO2 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 VO2 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. (AU)

• FAPESP's process: 07/58942-0 - From the bench to clinical trials: development of biomarkers as response predictors to therapy and target organs damage in systemic arterial hypertension
• Grantee: Eduardo Moacyr Krieger
• Support Opportunities: Research Projects - Thematic Grants