The Complexity of FGF23 Effects on Cardiomyocytes in Normal and Uremic Milieu.

Andreja Figurek,Goce Spasovski,Merita Rroji

doi:10.3390/cells10051266

Abstract

Fibroblast growth factor-23 (FGF23) appears to be one of the most promising biomarkers and predictors of cardiovascular risk in patients with heart disease and normal kidney function, but moreover in those with chronic kidney disease (CKD). This review summarizes the current knowledge of FGF23 mechanisms of action in the myocardium in the physiological and pathophysiological state of CKD, as well as its cross-talk to other important signaling pathways in cardiomyocytes. In this regard, current therapeutic possibilities and future perspectives are also discussed.

Highlights

The endocrine family consists of a unique structure lacking conserved heparin (HS)binding domain, which favors their release from the production source, disadvantaging their fibroblast growth factors (FGF) receptors (FGFR) activation at targeted organs
Data from the clinical studies support the important role of Fibroblast growth factor-23 (FGF23)/Klotho/Wnt pathway cross-talk, where it was shown that in patients on hemodialysis elevated serum
Experimental studies in rats pointed out that left ventricular fibrosis did not correlate with FGFR4 and nuclear factor of activated T-cells (NFAT) activation, indicating that the fibrotic process was not mediated through the activation of FGF23/FGFR4/calcineurin/NFAT pathway [85]

Summary

FGF23 Signaling in the Physiological Milieu

FGF23 Effects on Cardiomyocytes in FGF23 is a phosphaturic hormone primarily secreted by osteocytes to maintain phosphate and mineral homeostasis. The other possible mechanisms investigate the activation of RAAS through either suppression of 1.25 (OH2)D, which, in turn, increase the renin expression and reduction of ACE2 expression [39]; ectopic expression of FGF23 and αKlotho in the stressed myocardium and not in the normal heart [40]; and suppression of FGF23 of α-Klotho [41] that may lead to LVH through loss of the sKL cardioprotective effec [42]. The pro-hypertrophic effects of the prototypical paracrine FGF family member, FGF2, were blocked by inhibitors of the Ras (a small GTPase)/mitogen-activated protein kinase (Ras/MAPK) cascade. These effects on cardiomyopathy were independent of blood pressure levels. It was shown that FGF23 increases intracellular calcium levels in cardiac myocytes in vitro and promotes contractility of murine cardiac myocytes and ventricular muscle strips ex vivo independently from α-klotho

Cardiac Hypertrophy

Cardiac Fibrosis

Findings

Future Perspectives