Myocardial infarction (MI) is a major cause of death worldwide. Epidemiological studies have linked vitamin D deficiency to MI incidence and support a role of vitamin D signalling in the pathophysiology of MI. However, the mechanisms by which vitamin D may regulate cardiovascular function in MI are still controversial. 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 unrecognised pathophysiological factor causally linked to progression of cardiac dysfunction post-MI. To test our hypothesis, we induced experimental MI in two different rat and mouse animal models by permanent or transient ligation of the left descending coronary artery. Animals without ligation served as sham-operated controls. We show that circulating intact Fgf23 was profoundly elevated, whereas serum vitamin D hormone levels were suppressed after MI in rat and mouse models. Western blotting and immunohistochemical analysis revealed that both skeletal and cardiac expression of Fgf23 was increased after MI. Serum parathyroid hormone, phosphate, sodium, and calcium remained unchanged in MI animals. Since it has been suggested that the FGF23 co-receptor Klotho may have an FGF23 independent protective role in the regulation of cardiac function we measured the abundance of soluble Klotho by western blotting. However, serum Klotho remained unchanged in MI rats and mice. In conclusion, our study has uncovered that experimental MI causes a profound up-regulation in intact circulating Fgf23, independent of changes in serum soluble Klotho or serum parathyroid hormone. 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 which may have important clinical implications, and may inaugurate the new field of cardio-osteology.
Disclosure: The authors declared no competing interests. This work was supported by grants from the Austrian Science Fund to Olena Andrukhova (FWF P26534).