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Research Mentor and Department
In both humans and mice, Fibroblast Growth Factor (FGF) is upregulated following injury to the heart, and published studies have shown that FGF2 serves as a mediator in cardioprotection following cardiac stress or injury. Although FGF2 plays an important role following injury, mice that lack or overexpress FGF2 develop normally and do not have a phenotype under homeostatic conditions. It is currently unknown how FGF signaling is regulated in the adult heart and why the effects are only observed following injury. We hypothesized that FGF signaling may be repressed in the adult heart under homeostatic conditions and becomes reactivated following injury. A doxycycline-inducible, cardiomyocyte specific, constitutively-active FGF receptor mouse model (αMHC-rtTA, TRE-caFGFR1-myc) was utilized to test whether the cardiomyocyte has the capacity to respond to a cell autonomous FGF signal. Twelve- to 14-week old mice were fed doxycyline-containing (DOX) chow to induce caFGFR1 in cardiomyocytes. Histologic analysis showed significantly increased cardiomyocyte-cross sectional area in caFGFR1 hearts by one week following induction. Trichrome and H&E staining also indicated an increase in fibrosis and myocyte disarray in caFGFR1 hearts. These findings demonstrate that activation of FGF signaling in adult murine cardiomyocytes results in hypertrophic cardiomyopathy (HCM). The in vivo mechanisms by which FGF signaling affects cardiomycyte hypertrophy are currently under investigation.