Conditional deletion of FGFR4 in the myocardium prevented rFGF23-induced LVH in mice, establishing direct cardiotoxicity of FGF23 through activation of FGFR4.
Only the 20-week-old B6-Col4a3KO mice developed LVH (LV mass 125 ± 3 versus 98 ± 6 mg; P < 0.05 versus WT) in association with significantly increased cardiac expression of FGF receptor 4 (FGFR4) messenger RNA and protein and markers of LVH (Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), beta-myosin heavy chain (β-MHC); P < 0.05 versus WT for each).
A recent study identified fibroblast growth factor receptor 4 as the primary receptor mediating the effect of fibroblast growth factor 23 on left ventricular hypertrophy, providing new mechanistic insights and a potential therapeutic target to reduce cardiovascular morbidity in chronic kidney disease.
Mice lacking FGFR4 do not develop LVH in response to elevated FGF23, whereas knockin mice carrying an FGFR4 gain-of-function mutation spontaneously develop LVH.