Vascular endothelial growth factor (VEGF)-A: Role on cardiac angiogenesis following myocardial infarction

Abstract

The current study is to determine the regulatory role of VEGF-A in cardiac angiogenesis following myocardial infarction (MI). Cardiac angiogenic response and temporal/spatial expression of VEGF-A/VEGF receptors (VEGFR) were examined at 1, 2, 6, 12 hours and 1, 2, 3, 4, 7, 14, and 28 days postMI. We found that following MI, newly formed vessels first appeared at the border zone between noninfarcted and infarcted myocardium as early as day 3 and subsequently in the infarcted myocardium. Vascular density in the infarcted myocardium peaked at day 7 and then gradually declined. VEGF-A mRNA started to increase at the border zone at 2 hours postMI, reached peak at 12 hours, declined at day 1, and returned to normal levels at day 2 and thereafter. VEGF-A protein levels at the border zone were only increased during day 1 postMI. VEGF-A within the infarcted myocardium levels, however, were persistently suppressed postMI. VEGFR expression was significantly increased only at the border zone at day 1, but not in the later stages. The expression of VEGF-A/VEGFR remained unchanged in the noninfarcted myocardium. Thus, the early rise of VEGF-A/VEGFR at the border zone suggests that VEGF-A initiates the cardiac angiogenic response postMI, but short-lived VEGF-A/VEGFR activation at the border zone and consistently suppressed VEGF-A within the infarcted myocardium suggests that VEGF-A may not be crucial to the later stages of angiogenesis.

Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations

“…In the same year, the regulatory role of this cell factor was studied by Zhao et al 104 Two other ligands, nerve growth factor and myeloid-derived growth factor, have increased circulation levels after myocardial infarction and have been connected to postinjury myocardial regeneration. 105,106 Similar to other striated muscles, the injured cell milieu generated by the damage dictates the tropism of resident progenitor and stem cells to the injury site, mediating a certain degree of self-recovery, [103][104][105][106][107] but since the adult cardiomyocytes are known to be in mitotic arrest, this limits the repair mechanism.…”

“…105,106 Similar to other striated muscles, the injured cell milieu generated by the damage dictates the tropism of resident progenitor and stem cells to the injury site, mediating a certain degree of self-recovery, [103][104][105][106][107] but since the adult cardiomyocytes are known to be in mitotic arrest, this limits the repair mechanism. 108,109 Thus, considering the low regeneration potential of the endogenous mechanisms attempts to stimulate regeneration by using exogenous stem cells seem plausible.…”

WT1 in Cardiac Development and Disease

“…The extracellular matrix (ECM) is degraded ensuring infiltration of inflammatory cells, which remove the cellular debris generated during acute cardiac injury (40,41). The expression of WT1 in the epicardium is already upregulated 1 day after infarction and is induced throughout the entire In the infarcted area, an increase in granulation tissue is observed approximately 3 days after MI, which is characterized by the presence of interstitial fibroblasts, myofibroblasts, and forming blood vessels (12,14,43,46,47). As opposed to the expression in the subepicardium, upregulation of WT1 expression is present in endothelial cells and not in (myo) fibroblasts in the myocardial layer (14) (data not shown; Figure 4).…”

Endothelial cells overexpressing IL-8 receptor reduce cardiac remodeling and dysfunction following myocardial infarction

“…Several strategies including growth factor delivery (7,38), gene therapy (12), and cell-based therapy (25,33) have been developed to promote neovascularization in the ischemic myocardium. Among them, cell-based therapy has emerged as the most promising therapeutic tool for vascular growth and treatment of ischemic cardiovascular disease.…”