Physiological Role of FGF Signaling in Growth and Remodeling of Developing Cardiovascular System

Abstract

Fibroblast growth factor (FGF) signaling plays an important role during embryonic induction and patterning, as well as in modulating proliferative and hypertrophic growth in fetal and adult organs. Hemodynamically induced stretching is a powerful physiological stimulus for embryonic myocyte proliferation. The aim of this study was to assess the effect of FGF2 signaling on growth and vascularization of chick embryonic ventricular wall and its involvement in transmission of mechanical stretch-induced signaling to myocyte growth in vivo. Myocyte proliferation was significantly higher at the 48 h sampling interval in pressure-overloaded hearts. Neither Western blotting, nor immunohistochemistry performed on serial paraffin sections revealed any changes in the amount of myocardial FGF2 at that time point. ELISA showed a significant increase of FGF2 in the serum. Increased amount of FGF2 mRNA in the heart was confirmed by real time PCR. Blocking of FGF signaling by SU5402 led to decreased myocyte proliferation, hemorrhages in the areas of developing vasculature in epicardium and digit tips. FGF2 synthesis is increased in embryonic ventricular cardiomyocytes in response to increased stretch due to pressure overload. Inhibition of FGF signaling impacts also vasculogenesis, pointing to partial functional redundancy in paracrine control of cell proliferation in the developing heart.

New developments in the biology of fibroblast growth factors

“…In chicken embryos, inducing left ventricular pressure overload resulted in increased Fgf2 mRNA expression in the heart, increased levels of FGF2 in the serum, and increased myocyte proliferation. Pharmacological inhibition of FGFR signaling decreased myocyte proliferation and resulted in epicardial hemorrhages (Krejci et al, 2016).…”

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair

“…In the characterization of FGF superfamily member effects, a putative redundancy in the function of distinct FGF ligands (e.g., FGFs 3 and 8 with FGF10) and receptors (e.g., between FGFR1c and 2c in interaction with FGF9 subfamily) in the process of heart development and the adult phase needs to be considered ( Lavine et al, 2005 ; Marguerie et al, 2006 ; Watanabe et al, 2010 ; Urness et al, 2011 ; Krejci et al, 2016 ).…”

Conditioned medium of sympathetic ganglia with addition of fibroblast growth factor 2 promotes plasticity of cardiomyocytes in culture

“…The interaction of FGF-2 with the cardiomyocyte develops as a looping action, since the cardiomyocyte itself is capable of producing FGF-2, which will act on itself since embryogenesis, in addition to participating in angiogenesis (Krejci, Pesevski, Nanka & Sedmera, 2016). Evidence points to an apparently paradoxical function of FGF-2 and other FGF molecules in cardiogenesis itself, determining the differentiation of precursor cells in cardiomyocytes at early stages of development but preventing premature differentiation at later stages through action in the determination and control of cellular apoptosis (Zhang et al, 2012).…”