Effect of Fibroblast Growth Factor 2 on Extraocular Muscle Structure and Function

Introduction: Fibroblast growth factor 23 (FGF23), an endocrine hormone, induced left ventricular (LV) hypertrophy through direct action in experimental animal models. The association of FGF23 with echocardiographic measures in humans is relatively uncharacterized. Hypothesis: Higher levels of FGF23 will be cross-sectionally associated with more adverse echocardiographic measures of LV structure and function. Methods: We conducted a cross-sectional analysis of 2086 African-American adults (66% female, median age 55) from a subset of the ARIC Study, a community-based cohort in the United States. Intact active FGF23 was assessed in blood samples collected at ARIC visit two (1990-1992). Echocardiography was performed at visit three (1993-1995) in participants recruited at the Jackson field center only. We used multivariable linear regression to evaluate the associations of FGF23 (per 15 pg/mL change) with echocardiographic measures after adjustment for traditional cardiovascular risk factors assessed at visit two. We also examined differences in observed associations by age and sex using interaction terms. Results: FGF23 was significantly associated with greater left atrial diameter and LV mass index (Table). A significant sex interaction was identified for LV diameter (p-interaction = 0.005). No association was observed in men while a positive association was observed among women. An adverse, decreasing trend in percent fractional shortening of the LV diameter at higher levels of FGF was stronger in individuals aged >55 (p-interaction = 0.03). No linear association was found between FGF23 and E/A ratio. Conclusion: FGF23 was associated with higher LV mass, larger LV size, and lower LV systolic function. These findings are consistent with results from experimental animal studies and provide evidence suggesting that cardiac structure and function may be influenced by FGF23 in humans. Prospective studies are needed to evaluate whether FGF23 is associated with change in markers of cardiac structure and function.

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Modulation of Human Valve Interstitial Cell Phenotype and Function Using a Fibroblast Growth Factor 2 Formulation

PLoS ONE ◽

10.1371/journal.pone.0127844 ◽

2015 ◽

Vol 10 (6) ◽

pp. e0127844 ◽

Cited By ~ 33

Author(s):

Najma Latif ◽

Alfred Quillon ◽

Padmini Sarathchandra ◽

Ann McCormack ◽

Alec Lozanoski ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Interstitial Cell ◽

Fibroblast Growth Factor 2 ◽

Cell Phenotype ◽

Fibroblast Growth ◽

And Function

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Fibroblast growth factor homologous factors: Evolution, structure, and function

Cytokine & Growth Factor Reviews ◽

10.1016/j.cytogfr.2005.02.002 ◽

2005 ◽

Vol 16 (2) ◽

pp. 215-220 ◽

Cited By ~ 126

Author(s):

Mitchell Goldfarb

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Structure And Function ◽

Fibroblast Growth ◽

And Function

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Fibroblast growth factor 2 (FGF-2) differentially regulates connexin (cx) 43 expression and function in astroglial cells from distinct brain regions

Glia ◽

10.1002/(sici)1098-1136(199801)22:1<19::aid-glia3>3.0.co;2-3 ◽

1998 ◽

Vol 22 (1) ◽

pp. 19-30 ◽

Cited By ~ 52

Author(s):

Bernhard Reuss ◽

Rolf Dermietzel ◽

Klaus Unsicker

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Brain Regions ◽

Fibroblast Growth Factor 2 ◽

Fibroblast Growth ◽

Astroglial Cells ◽

And Function ◽

Cx 43

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Thrombospondin 1 as a scavenger for matrix-associated fibroblast growth factor 2

Blood ◽

10.1182/blood-2003-03-0893 ◽

2003 ◽

Vol 102 (13) ◽

pp. 4399-4406 ◽

Cited By ~ 57

Author(s):

Barbara Margosio ◽

Daniela Marchetti ◽

Veronica Vergani ◽

Raffaella Giavazzi ◽

Marco Rusnati ◽

...

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Angiogenic Factors ◽

Fibroblast Growth Factor 2 ◽

Fibroblast Growth ◽

Heparin Binding ◽

Factors Affecting ◽

Thrombospondin 1 ◽

And Function

AbstractThe antiangiogenic factor thrombospondin 1 (TSP-1) binds with high affinity to several heparin-binding angiogenic factors, including fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), and hepatocyte growth factor/scatter factor (HGF/SF). The aim of this study was to investigate whether TSP-1 affects FGF-2 association with the extracellular matrix (ECM) and its bioavailability. TSP-1 prevented the binding of free FGF-2 to endothelial cell ECM. It also promoted the mobilization of matrix-bound FGF-2, generating a TSP-1/FGF-2 complex. The region of TSP-1 responsible for these activities was located within the 140-kDa antiangiogenic and FGF-2 binding fragment, whereas the 25-kDa heparin-binding fragment was inactive. Matrix-released FGF-2/TSP-1 complex had a reduced ability to bind to and induce proliferation of endothelial cells. TSP-1 depleted the ECM laid by FGF-2-overproducing tumor cells of its FGF-2-dependent mitogenic activity for endothelial cells. Besides FGF-2, TSP-1 also inhibited VEGF and HGF/SF binding to the ECM and mobilized them from the ECM. Our study shows that TSP-1 acts as a scavenger for matrix-associated angiogenic factors, affecting their location, bioavailability, and function. (Blood. 2003; 102:4399-4406)

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