Structural stability of neoangiogenic intramyocardial microvessels supports functional recovery in chronic ischemic myocardium

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 o...

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Veröffentlicht in:Journal of molecular and cellular cardiology 2008-07, Vol.45 (1), p.70-80
Hauptverfasser: Shim, Winston S.N, Lim, Sze Yun, Li, Shi Qi, Gu, Yacui, Ong, Hwee Choo, Song, In Chin, Chuah, Seng Chye, Wong, Philip
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Sprache:eng
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Zusammenfassung: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.
ISSN:0022-2828
1095-8584
DOI:10.1016/j.yjmcc.2008.04.007