Temporal and Spatial Activation of Angiogenesis and Expression of VEGF/VEGF Receptors in the Infarcted Heart

Abstract

We sought to determine temporal and spatial expression of VEGF/VEGF receptors and their relation to angiogenesis in the infarcted heart. Hearts were collected at hour 3, 6, 12, day 1, 3, 5, 7, 14, 21 and 28 postMI. Normal rats served as controls. Cardiac VEGF gene and protein expression, VEGFR and angiogenesis were examined. After MI, existing vessels were lost in the infarcted myocardium at day 1 postMI. Newly formed vessels first appeared at the border zone as early as day 3, followed by the infarcted myocardium. Vascular density peaked at day 7 and 14, and gradually declined at day 21 and 28. VEGF gene expression was largely increased in the border zone from hour 6 to day 4, but not in the later stage, while it was markedly reduced within the infarcted myocardium at all time points. VEGF protein expression was evident at the border zone, while it was largely decreased in the infarcted myocardium at all time points. VEGF receptor binding was significantly lowered in the infarcted myocardium in the first week and gradually increased thereafter. The expression of VEGF and VEGF receptors remained unchanged in noninfarcted myocardium. Thus, angiogenesis is activated in the infarcted myocardium in the early stage of MI and becomes quiescent thereafter. VEGF expression is elevated soon after MI at the border zone, but not in the late stage of MI. The early rise in VEGF in the border zone may trigger cardiac angiogenesis following MI.