VEGF and bFGF stimulate myocardial vascularization in embryonic chick

Abstract

We tested the hypothesis that early vascularization of the embryonic heart is enhanced after bolus injections of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) into the vitelline vein before the onset of myocardial vasculogenesis (3.5 days, stage 21). Electron and light microscopy were utilized to obtain morphometric data. At stages 29 and 31, myocardial vessel volume or numerical density were higher in embryos injected with 50 ng bFGF than in the saline-injected controls. A VEGF injection increased vascular volume density at stage 29 and both volume and numerical density at stage 31. bFGF, but not VEGF, was associated with an enhancement of the sinusoidal system (spongy layer of the ventricle) at stage 29. This effect disappeared by stage 31. In conclusion, 1) enhancement of bFGF or VEGF before myocardial vascularization increases vascular growth, but the initial effect of bFGF is greater; 2) the effects of these growth factors on vascular volume and numerical density are temporally dependent; and 3) bFGF, in addition to its effects on the coronary vasculature, influences ventricular modeling by apparently acting on myocytes as well as endothelial cells.

The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells

“…The commitment of EPDCs into the angioblastic lineage seems to be under the control of the myocardial production of VEGF and bFGF (Tomanek et al, 1998(Tomanek et al, , 1999(Tomanek et al, , 2002Wessels et al, unpublished). VEGF is generally considered to regulate vascular differentiation and morphogenesis via VEGFR-2, although it is not clear if it is indispensable for angioblastic specification and differentiation (Vokes and Krieg, 2002).…”

“…Actually, the myocardial synthesis of fibronectin seems to precede the arrival of the epicardial cells to the myocardium (Ká lmá n et al, 1995) and may play a role in directing epicardial migration. The subepicardium also accumulates growth factors such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) (Tomanek et al, 1998(Tomanek et al, , 1999(Tomanek et al, , 2002Zheng et al, 2001) and is likely to retain other myocardially secreted growth factors like hepatocyte growth factor (HGF) (Rappolee et al, 1996;Song et al, 1999), transforming growth factors (TGF␤s), and bone morphogenetic proteins (BMPs) (Yamagishi et al, 1999;Nakajima et al, 2000). The release of these factors appears to be partially controlled by the interactions with the matrix.…”

Cardiac Vasculature: Development and Pathology

“…Thus, the availability of VEGF may play a role in determining whether the phenotype of the growing heart is "physiological" or "pathological" (Shiojima I et al, 2005). In addition to the VEGF family, bFGF and angiopoietins play major roles in myocardial vascularization (Tomanek RJ et al, 1998;Visconti RP et al, 2002). It was recently demonstrated that angiogenesis can induce myocardial hypertrophy even in the absence of a hemodynamic stimulus (Tirziu D et al, 2007).…”

Deficiency in endothelial nitric oxide synthase impairs myocardial angiogenesis

“…Neonatal widetype C57BL/6 and eNOS Ϫ/Ϫ mice at postnatal day 1 were used for stereology analysis of myocardial capillary vasculature similar to previously described methods (29) with modifications. Under a stereomicroscope, the chest was opened from the sternum.…”