Experimental Myocardial Infarction Upregulates Circulating Fibroblast Growth Factor-23

Abstract

Myocardial infarction (MI) is a major cause of death worldwide. Epidemiological studies have linked vitamin D deficiency to MI incidence. Because fibroblast growth factor‐23 (FGF23) is a master regulator of vitamin D hormone production and has been shown to be associated with cardiac hypertrophy per se, we explored the hypothesis that FGF23 may be a previously unrecognized pathophysiological factor causally linked to progression of cardiac dysfunction post‐MI. Here, we show that circulating intact Fgf23 was profoundly elevated, whereas serum vitamin D hormone levels were suppressed, after induction of experimental MI in rat and mouse models, independent of changes in serum soluble Klotho or serum parathyroid hormone. Both skeletal and cardiac expression of Fgf23 was increased after MI. Although the molecular link between the cardiac lesion and circulating Fgf23 concentrations remains to be identified, our study has uncovered a novel heart–bone–kidney axis that may have important clinical implications and may inaugurate the new field of cardio‐osteology. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).

Strength of Fibroblast Growth Factor 23 as a Cardiovascular Risk Predictor in Chronic Kidney Disease Weaken by ProBNP Adjustment

“…At that time, FGF23 was majorly considered to be regulated by other CKD-MBD components, such as high vitamin D, high parathyroid hormone and high phosphorus [21]. In contrast, we learnt in recent years that regulators outside such classical CKD-MBD pathways (in the following referred to as "non-CKD-MBD regulators") may substantially contribute to FGF23 regulation, among which iron deficiency [22] and prevalent heart disease [23] may be of particular importance.…”

“…FGF23 may reflect prevalent cardiovascular disease [2]. This concern has been founded upon the observation that hypertrophic and failing [20,23,28] hearts may directly produce FGF23, that particularly high FGF23 levels are found in patients with severe acute heart disease [38,39], and that patients chronically exposed to high FGF23 -such as patients with hypophosphatemic rickets/osteomalacia -do not regularly develop heart disease [40]. Experimentally, a direct role of FGF23 in the development of vascular calcification has largely been ruled out [41], and data on its contribution to left ventricular hypertrophy remains uncertain: even though several reports have suggested FGF23 to activate cardiomyocytes and induce their proliferation [8,9], later studies have questioned these findings [15][16][17][18][19][20].…”

Changes in Serum Fibroblast Growth Factor 23 in Patients With Acute Myocardial Infarction

“…It should be noted, however, that Andrukhova et al also showed in their animal study that serum FGF23 increased 2-4 weeks after reperfusion. 15 Last, we cannot conclude which of the 3 observations (i.e., absolute value of FGF23 on admission, absolute value on day 7, and relative FGF23 increase on day 7) will have the most significant clinical importance, because, in the current study, only a small number of patients was enrolled, and whether or not the serum FGF23 level on admission was decreased among patients with AMI could not be definitively determined.…”

“…In an animal model of MI and subsequent reperfusion, elevation of the serum FGF23 level was demonstrated at 2-and 4-weeks post-MI, although whether or not it had changed at earlier time points was not reported. 15 These findings collectively raise the possibility that the alteration in the serum FGF23 level may be related to various cardiac injury or hemodynamic alterations.…”

“…13, 14 Notably, cardiac FGF23 expression and serum FGF23 levels were found to be increased in a rodent model of myocardial infarction (MI). 15 Considering that higher levels of circulating FGF23 predict aggravated left ventricular (LV) remodeling after reperfusion of acute MI (AMI) in humans, 12 how the serum FGF23 concentration, as well as cardiac FGF23 expression, is regulated in patients with AMI may provide important clinical information. To this end, we investigated whether serum FGF23 levels are altered in patients diagnosed with AMI and, if so, what factors are related to the changes in serum FGF23 in these patients.…”