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Title: Structural stability of neoangiogenic intramyocardial microvessels supports functional recovery in chronic ischemic myocardium
Authors: Shim, W.S.N. 
Lim, S.Y.
Li, S.Q.
Gu, Y.
Ong, H.C.
Song, I.C.
Chuah, S.C.
Wong, P.
Keywords: Ischemia
Myocardial contractility
Vascular adaptation
Vascular stability
Issue Date: Jul-2008
Citation: Shim, W.S.N., Lim, S.Y., Li, S.Q., Gu, Y., Ong, H.C., Song, I.C., Chuah, S.C., Wong, P. (2008-07). Structural stability of neoangiogenic intramyocardial microvessels supports functional recovery in chronic ischemic myocardium. Journal of Molecular and Cellular Cardiology 45 (1) : 70-80. ScholarBank@NUS Repository.
Abstract: We hypothesize that combining angiopoietin-1 (ANG-1) or ANG-2 with vascular endothelial growth factor (VEGF) improves myocardial perfusion and contractile function by modulating vascular adaptation of neoangiogenic microvessels in a chronic ischemic swine model. Four weeks after occlusion of the left circumflex coronary artery (LCx), animals were injected with AdVEGF165 (n = 6), AdVEGF165+AdANG-1 (n = 6), AdVEGF165+AdANG-2 (n = 6) or control vector (n = 5) into the left ventricular posterolateral wall. Regional perfusion by fluorescent microspheres and segmental myocardial tissue velocity by tissue Doppler imaging (TDI) were assessed at baseline, 4 weeks post occlusion and 4 weeks post therapy. Despite similar vascular growth following VEGF+ANG-1 and VEGF+ANG-2 treatments, transmural myocardial contractility improved only when VEGF was paired with ANG-1. In contrast, regional systolic function deteriorated uniformly across subepicardial, mid-myocardial and subendocardial segments in VEGF and VEGF+ANG-2 treated groups. Contractile improvement was associated with enhanced vascular stability through augmented arteriole formation, tight structural integration between VE-cadherin and β-catenin at endothelial junctions and improved cross-talk between endothelium and myocardium. Structural stability of developing intramyocardial microvessels contributes to systolic function during ischemic neovascularization. Coordinated regulation of angiogenic revascularization that supports vascular stability is a key aspect in improving therapeutic outcomes in ischemic myocardium. © 2008 Elsevier Inc. All rights reserved.
Source Title: Journal of Molecular and Cellular Cardiology
ISSN: 00222828
DOI: 10.1016/j.yjmcc.2008.04.007
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