Garcia MI, Karlstaedt A, Amione-Guerra J, Youker KA, Taegtmeyer H, Boehning D (2016) Functionally redundant control of cardiac hypertrophic signaling by inositol 1,4,5-trisphosphate receptors. Higazi DR, Fearnley CJ, Drawnel FM, Talasila A, Corps EM, Ritter O, McDonald F, Mikoshiba K, Bootman MD, Roderick HL (2009) Endothelin-1-stimulated InsP3-induced Ca 2+ release is a nexus for hypertrophic signaling in cardiac myocytes. ĭewenter M, Von Der Lieth A, Katus HA, Backs J (2017) Calcium signaling and transcriptional regulation in cardiomyocytes. Ljubojevic S, Radulovic S, Leitinger G, Sedej S, Sacherer M, Holzer M, Winkler C, Pritz E, Mittler T, Schmidt A, Sereinigg M, Wakula P, Zissimopoulos S, Bisping E, Post H, Marsche G, Bossuyt J, Bers DM, Kockskämper J, Pieske B (2014) Early remodeling of perinuclear Ca 2+ stores and nucleoplasmic Ca2 2+ signaling during the development of hypertrophy and heart failure. ĭickhout JG, Carlisle RE, Austin RC (2011) Interrelationship between cardiac hypertrophy, heart failure, and chronic kidney disease: endoplasmic reticulum stress as a mediator of pathogenesis. Nakayama H, Bodi I, Maillet M, Desantiago J, Domeier TL, Mikoshiba K, Lorenz JN, Blatter LA, Bers DM, Molkentin JD (2010) The IP3 receptor regulates cardiac hypertrophy in response to select stimuli. These findings indicate a pathophysiological role of the cellular angiotensin system in FGF23-induced hypertrophy in ventricular cardiomyocytes. FGF23-mediated cellular hypertrophy is associated with increased production and secretion of ATII by cardiomyocytes. In conclusion, FGF23 and ATII share a common mechanism of IP3-nuclear Ca 2+-dependent cardiomyocyte hypertrophy. In addition, application of FGF23 increased intracellular expression of ATII peptide and its secretion in NRVMs, confirming the participation of ATII. Interestingly, ATII receptor antagonist, losartan, significantly attenuated FGF23-induced changes in Ca 2+ homeostasis and cellular hypertrophy suggesting an involvement of ATII receptor-mediated signaling. In addition to a global increase in cytoplasmic Ca 2+, FGF23, like ATII, induced inositol 1, 4, 5-triphosphate (IP3)-induced Ca 2+ release from the nucleoplasmic Ca 2+ store, associated with cellular hypertrophy. Furthermore, FGF23 activates nuclear Ca 2+-regulated CaMKII–HDAC4 pathway, similar to ATII. In neonatal rat ventricular myocytes (NRVMs), both ATII and FGF23 induced hypertrophy as observed by an increase in cell area and hypertrophic gene expression. In the present study, we investigated Ca 2+-dependent signaling of FGF23 in ventricular cardiomyocytes and its association with angiotensin II (ATII). FGF23 is proposed to trigger pathological signaling mediated by Ca 2+-regulated transcriptional pathways. In vivo, high circulating levels of FGF23 are associated with an altered systemic RAAS response. It is also a mediator of left-ventricular hypertrophy (LVH). Fibroblast growth factor 23 (FGF23), an endocrine hormone, is linked to HF and cardiovascular mortality. Heart failure (HF) manifestation and progression are driven by systemic activation of neuroendocrine signaling cascades, such as the renin–angiotensin aldosterone system (RAAS).

Pathological hypertrophy heart diagram