Abstract
ObjectiveElevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular events, particularly heart failure. Although FGF23 has been reported to induce cardiac hypertrophy, recent studies demonstrated that cardiac hypertrophy and myocardial infarction induce FGF23 production by cardiomyocytes. We aimed to explore whether acute cardiac overload increases cardiac and skeletal FGF23 expression and circulating FGF23 levels.MethodsWe administered 30 μL/g bodyweight of isotonic saline intraperitoneally in rats to induce acute cardiac overload. We measured serum FGF23 levels and other parameters of mineral metabolism at 2, 6, and 24 h after saline or sham injection. We also analyzed gene expression in the heart, calvarium, femur, and kidney at 2 and 24 h after injection.ResultsAcute saline injection induced cardiac overload as evidenced by a significant upregulation of brain natriuretic peptide along with a trend towards increased expression of atrial natriuretic peptide and mild hyponatremia. However, there were no changes in serum FGF23 levels or FGF23 expression in the heart, calvarium, or femur.ConclusionsAcute cardiac overload by saline injection in rats did neither induce FGF23 expression in the heart or bone nor did it increase serum FGF23 levels. These findings suggest that more severe or long-term cardiac damage is required for induction of FGF23 expression.
Highlights
Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a major role in the regulation of phosphate and vitamin D metabolism
There were no changes in serum FGF23 levels or FGF23 expression in the heart, calvarium, or femur
Recent investigations demonstrated that cardiomyocytes are the source of FGF23 in animal models of myocardial infarction [22] and cardiac hypertrophy induced by transverse aortic constriction or cardiomyocyte-specific activation of calcineurin A [23]
Summary
Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a major role in the regulation of phosphate and vitamin D metabolism. FGF23 primarily acts on the kidneys to induce urinary phosphate excretion by downregulating the sodium-dependent phosphate cotransporters Napi2a and Napi2c and suppress 1,25-dihydroxyvitamin D [1,25(OH) D] synthesis by altering the vitamin D-metabolizing enzymes CYP27b1 and CYP24a1 [1,2,3]. These functions of FGF23 are mediated by binding to FGF receptor 1 (FGFR1) and the transmembrane protein Klotho, which forms a specific receptor complex for FGF23 [4,5]. Elevated FGF23 has been linked to volume overload, a common manifestation of heart failure [16,17,18].
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