Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling
J. Clin. Invest. Julian C. Braz, et al. 111:1475 doi:10.1172/JCI17295 [Go to this article.]

Figure 2
Dnp38α, dnMKK3, and dnMKK6 transgenic mice show progressive cardiac hypertrophy at baseline. (a) Heart-to-body weight ratio (HW/BW) measurements at 2, 4, and 8 months of age show a progressive increase in heart size in dnp38α, dnMKK3, and dnMKK6 transgenic mice compared with nontransgenics. Four animals were assayed at 2 and 4 months, while six animals were measured at 8 months in each group. (b) Measurement of left ventricular diastolic dimension (LVED) by echocardiography shows progressive cardiac dilation over time in dnp38α, dnMKK3, and dnMKK6 transgenic mice (n = 4 each group). (c) Measurement of ANF and BNP mRNA levels in nontransgenic and transgenic hearts at 2 months of age averaged from four independent hearts. (d) Macroscopic histological analysis of H&E-stained hearts from dnp38α, dnMKK3, and dnMKK6 transgenic mice at 4 months of age (top panels) shows increased heart size in the transgenic mice. The middle panels show Masson’s trichrome staining at 4 months (×200), which reveals interstitial cell fibrosis in dnp38α and dnMKK3 transgenic hearts (blue). Histological sections were also stained with wheat germ agglutinin-TRITC conjugate (bottom panels) to permit quantitation (e) of myocyte cross-sectional areas (n = 200 cells per section) (*P < 0.05 versus nontransgenic mice).