Fibroblast growth factor-2 mediates pressure-induced hypertrophic response

In vitro, fibroblast growth factor-2 (FGF2) has been implicated in cardiomy ocyte growth and reexpression of fetal contractile genes, both markers of h ypertrophy. However, its in vivo role in cardiac hypertrophy during pressur e overload is not well characterized. Mice with or without FGF2 (Fgf2(+/+) and Fgf2(-/-), respectively) were subjected to transverse aortic coarctatio n (AC). Left ventricular (LV) mass and wall thickness were assessed by echo cardiography preoperatively and once a week postoperatively for 10 weeks. I n vivo LV function during dobutamine stimulation, cardiomyocyte cross-secti onal area, and recapitulation of fetal cardiac genes were also measured. AC Fgf2(-/-) mice develop significantly less hypertrophy (4-24% increase) com pared with AC Fgf2(+/+) mice (41-52% increase). Cardiomyocyte cross-section al 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(+/+) a nd Fgf2(-/-) hearts indicates a hypertrophic response of cardiomyocytes. Co nsequently, FGF2 plays a major role in cardiac hypertrophy. Comparison of a lpha- and beta-cardiac myosin heavy chain mRNA and protein levels in NC and AC Fgf2(+/+) and Fgf2(-/-) mice indicates that myosin heavy chain composit ion depends on hemodynamic stress rather than on FGF2 or hypertrophy, and t hat isoform switching is transcriptionally, not posttranscriptionally, regu lated.