FIGURE 4.

The ablation of TIGAR increases capillary density and coronary flow reserve (CFR) and attenuated cardiac hypertrophy and dysfunction in stressed hearts. (a) Representative immunoblots and densitometry analysis of TIGAR, Ang-1, VEGF, PFKFB3, β-MHC, and corresponding GAPDH or β-tubulin in the WT and TIGAR KO mice 8 weeks after TAC surgery. n = 4. **p < .01, ***p < .001, ****p < .0001. (b) The representative images of Isolectin B4 (IB4, green; DAPI stains the nuclei, blue)-stained frozen heart sections and quantification of the number of capillaries/100 nuclei 8 weeks after TAC surgery (n = 3). ***p < .001. Bar = 50 μm. (c) The representative pulsed-wave Doppler images of the proximal left coronary arteries of WT and TIGAR KO mice 8 weeks after TAC surgery. CFR gradually decreased in the WT mice, but it was not changed in the TIGAR KO mice (n = 8–18). *p < .05 versus corresponding WT mice, ^#p < .05 versus WT baseline. (d) Ratio of heart weight to tibia length in the WT and TIGAR KO mice 8 weeks after TAC surgery (n = 8). ****p < .0001. (e) The representative images of wheat germ agglutinin-stained frozen heart sections in the WT and TIGAR KO mice 8 weeks after TAC surgery. Cardiomyocyte hypertrophy is evident, as assessed by cross-sectional areas in the indicated groups. Bar = 50 μm. A minimum of 100 cardiomyocytes from each LV section of each mouse was measured (n = 4). **p < .01. (f) The representative echocardiographic images of WT and TIGAR KO mice subjected to TAC procedure for 8 weeks and the time course of left ventricular (LV) mass, ejection fraction (EF), and fractional shortening (FS) during the 8 weeks of pressure overload (n = 8–18). *p < .05 versus corresponding WT mice, ^#p < .05 versus WT baseline, ^†p < .05 versus TIGAR KO baseline. KO, knockout; TIGAR, TP53-induced glycolysis and apoptosis regulator; WT, wild type