Figure 7: ANGPTL2 down-regulation in heart blocks progression to HF.

(a–c) Representative immunoblot and quantitation of ANGPTL2 (a), relative levels of PGC-1α and PPARα transcripts (b) and levels of AKT and SERCA2a proteins (c) in hearts of WT mice 2 weeks after intravenous injection of 1 × 10¹⁰ or 3 × 10¹⁰ vg per mouse of AAV6-shAngptl2-A or -B relative to uninjected controls. Values from uninjected mice without were set to 1. n=4 per group. (d) Time line for AAV6-shAngptl2-B treatment and echocardiography analysis in the TAC model, 8–10 per group. (e) Representative western blot and quantitation of ANGPTL2 in TAC-induced hypertrophied heart, 4 weeks after injection of 3 × 10¹⁰ vg per mouse of AAV6-shScramble or 1 × 10¹⁰ or 3 × 10¹⁰ vg per mouse of AAV6-shAngptl2-B. (f–h) Comparison of indicated parameters among mice injected with 3 × 10¹⁰ vg per mouse of AAV6-shScramble or 1 × 10¹⁰ or 3 × 10¹⁰ vg per mouse of AAV6-shAngptl2-B. (i) Representative M-mode echocardiography recordings (upper), HE-stained sections of heart mid-portion (middle, Scale bar, 1 mm) and gross appearance of whole heart (bottom) in sham animals, and in TAC animals 4 weeks after injection of AAV6-shScramble or AAV6-shAngptl2-B (1 × 10¹⁰ or 3 × 10¹⁰ vg per mouse). Ruler tick marks indicate 1 mm. (j) HW/BW ratios of animals in h. (k) Relative expression of genes associated with HF. Control values from sham surgeries were set to 1 (e,k). Hsc70 served as a loading control. Data are means±s.e.m. Statistical significance was determined by one-way (a–c,e,g,h,j,k) or two-way (f) ANOVA. *P<0.05, **P<0.01, ^†P<0.001.