Fibroblast growth factor-2 mediates pressure-induced hypertrophic response.
In vitro, fibroblast growth factor-2 (FGF2) has been implicated in cardiomyocyte growth and reexpression of fetal contractile genes, both markers of hypertrophy. However, its in vivo role in cardiac hypertrophy during pressure overload is not well characterized. Mice with or without FGF2 (Fgf2(+/+) and Fgf2(-/-), respectively) were subjected to transverse aortic coarctation (AC). Left ventricular (LV) mass and wall thickness were assessed by echocardiography preoperatively and once a week postoperatively for 10 weeks. In vivo LV function during dobutamine stimulation, cardiomyocyte cross-sectional area, and recapitulation of fetal cardiac genes were also measured. AC Fgf2(-/-) mice develop significantly less hypertrophy (4-24% increase) compared with AC Fgf2(+/+) mice (41-52% increase). Cardiomyocyte cross-sectional area is significantly reduced in AC Fgf2(-/-) mice. Noncoarcted (NC) and AC Fgf2(-/-) mice have similar beta-adrenergic responses, but those of AC Fgf2(+/+) mice are blunted. A lack of mitotic growth in both AC Fgf2(+/+) and Fgf2(-/-) hearts indicates a hypertrophic response of cardiomyocytes. Consequently, FGF2 plays a major role in cardiac hypertrophy. Comparison of alpha- and beta-cardiac myosin heavy chain mRNA and protein levels in NC and AC Fgf2(+/+) and Fgf2(-/-) mice indicates that myosin heavy chain composition depends on hemodynamic stress rather than on FGF2 or hypertrophy, and that isoform switching is transcriptionally, not posttranscriptionally, regulated.
Schultz
J E
JE
Department of Molecular Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Witt
S A
SA
Nieman
M L
ML
Reiser
P J
PJ
Engle
S J
SJ
Zhou
M
M
Pawlowski
S A
SA
Lorenz
J N
JN
Kimball
T R
TR
Doetschman
T
T
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology*; D004280:Dobutamine / Q000494:pharmacology; D004452:Echocardiography; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D011312:Pressure
D016222:Fibroblast Growth Factor 2; D004280:Dobutamine; D018995:Myosin Heavy Chains