Abstract
Cardiac remodeling progresses to heart failure, which represents a major cause of morbidity and mortality. Cardiomyokines, cardiac secreted proteins, may play roles in cardiac remodeling. Fibroblast growth factors (FGFs) are secreted proteins with diverse functions, mainly in development and metabolism. However, some FGFs play pathophysiological roles in cardiac remodeling as cardiomyokines. FGF2 promotes cardiac hypertrophy and fibrosis by activating MAPK signaling through the activation of FGF receptor (FGFR) 1c. In contrast, FGF16 may prevent these by competing with FGF2 for the binding site of FGFR1c. FGF21 prevents cardiac hypertrophy by activating MAPK signaling through the activation of FGFR1c with β-Klotho as a co-receptor. In contrast, FGF23 induces cardiac hypertrophy by activating calcineurin/NFAT signaling without αKlotho. These FGFs play crucial roles in cardiac remodeling via distinct action mechanisms. These findings provide new insights into the pathophysiological roles of FGFs in the heart and may provide potential therapeutic strategies for heart failure.
Highlights
Heart failure represents a major cause of morbidity and mortality and remains a critical health problem
FGF2 effectively activates FGFR1c with heparin/heparin sulfate in non-cardiac cell types (Zhang et al, 2006). These findings do not necessary mean that FGFR1c is a FGF2 receptor in the heart, FGF2 might act on cardiac cells in a paracrine manner and promotes cardiac remodeling by activating MAPK signaling through the activation of FGFR1c (Table 1)
The heart appears to be a target of locally generated FGF21, even though FGF21 is an endocrine Fibroblast growth factors (FGFs). Both Fgfr1c and β-Klotho are predominantly expressed in cardiomyocytes. These findings indicate that FGF21 acts on cardiomyocytes possibly in a paracrine manner and prevents cardiac hypertrophy by activating MAPK signaling through the activation of FGFR1c with β-Klotho (Table 1) (Planavila et al, 2013)
Summary
Cardiomyokines, cardiac secreted proteins, may play roles in cardiac remodeling. Some FGFs play pathophysiological roles in cardiac remodeling as cardiomyokines. FGF2 promotes cardiac hypertrophy and fibrosis by activating MAPK signaling through the activation of FGF receptor (FGFR) 1c. FGF21 prevents cardiac hypertrophy by activating MAPK signaling through the activation of FGFR1c with β-Klotho as a co-receptor. FGF23 induces cardiac hypertrophy by activating calcineurin/NFAT signaling without αKlotho. These FGFs play crucial roles in cardiac remodeling via distinct action mechanisms. These findings provide new insights into the pathophysiological roles of FGFs in the heart and may provide potential therapeutic strategies for heart failure
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
