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 β-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 α- and β-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.
Jo El J. Schultz, Sandra A. Witt, Michelle L. Nieman, Peter J. Reiser, Sandra J. Engle, Ming Zhou, Sharon A. Pawlowski, John N. Lorenz, Thomas R. Kimball, Thomas Doetschman
Title and authors | Publication | Year |
---|---|---|
Sequence Analysis of the Fibroblast Growth Factor 2 Gene from the Spontaneously Hypertensive and Hypertrophic Heart Rats
JP Dwyer, V Kostka, SB Harrap, RD Nicolantonio |
Clinical and Experimental Hypertension | 2004 |
Ontogeny of Vascular Growth Factors in Perinatal Sheep Myocardium
TL van Natta, JC Ralphe, CE Mascio, KA Bedell, TD Scholz, JL Segar |
Journal of the Society for Gynecologic Investigation | 2004 |
Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity
JE Schultz, BJ Glascock, SA Witt, ML Nieman, KJ Nattamai, LH Liu, JN Lorenz, GE Shull, TR Kimball, M Periasamy |
American journal of physiology. Heart and circulatory physiology | 2004 |
The Physiological Genomics of the Critically Ill Mouse
C Ince |
2004 |