Intramyocardial VEGF-B 167 Gene Delivery Delays the Progression Towards Congestive Failure in Dogs With Pacing-Induced Dilated Cardiomyopathy
- 25 June 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 106 (12), 1893-1903
- https://doi.org/10.1161/circresaha.110.220855
Abstract
Rationale: Vascular endothelial growth factor (VEGF)-B selectively binds VEGF receptor (VEGFR)-1, a receptor that does not mediate angiogenesis, and is emerging as a major cytoprotective factor. Objective: To test the hypothesis that VEGF-B exerts non-angiogenesis-related cardioprotective effects in nonischemic dilated cardiomyopathy. Methods and Results: AAV-9-carried VEGF-B167 cDNA (1012 genome copies) was injected into the myocardium of chronically instrumented dogs developing tachypacing-induced dilated cardiomyopathy. After 4 weeks of pacing, green fluorescent protein-transduced dogs (AAV-control, n=8) were in overt congestive heart failure, whereas the VEGF-B-transduced (AAV-VEGF-B, n=8) were still in a well-compensated state, with physiological arterial Po2. Left ventricular (LV) end-diastolic pressure in AAV-VEGF-B and AAV-control was, respectively, 15.0±1.5 versus 26.7±1.8 mm Hg and LV regional fractional shortening was 9.4±1.6% versus 3.0±0.6% (all P167 exerted a compensatory receptor stimulation. The cytoprotective effects of VEGF-B167 were further elucidated in cultured rat neonatal cardiomyocytes exposed to 10−8 mol/L angiotensin II: VEGF-B167 prevented oxidative stress, loss of mitochondrial membrane potential, and, consequently, apoptosis. Conclusions: We determined a novel, angiogenesis-unrelated cardioprotective effect of VEGF-B167 in nonischemic dilated cardiomyopathy, which limits apoptotic cell loss and delays the progression toward failure.Keywords
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