Figure 2: Cardiomyocyte-derived ANGPTL2 induces cardiac dysfunction in mice.

(a) Shown are representative M-mode echocardiography recordings (upper row), left ventricle sections stained with wheat germ agglutinin (WGA; as an indicator of cardiomyocyte size) (middle, Scale bars, 50 μm) and DAPI staining (lower, Scale bars, 200 μm) of 6- and 12-week-old αMHC-Angptl2 Tg and littermate WTWT mice. (b) Diastolic left ventricular posterior wall thickness (LVPW;d), left ventricular end-diastolic internal diameter (LVID;d) and percent fractional shortening (%FS) in 6-, 12- and 18-week-old αMHC-Angptl2 Tg and WT mice (n=5–7 per group). (c) Relative expression of genes associated with HF and fibrosis in hearts of 12-week-old αMHC-Angptl2 Tg relative to littermate mice. WT values were set to 1 (n=5–7 per group). (d) Percentage of shortening of cardiomyocytes isolated from αMHC-Angptl2 Tg (n=31, N=3) and littermate WT mice (n=40, N=3). (e) Mean Ca²⁺ transients at 1 Hz stimulation, (f) peak amplitude of Ca²⁺ transients, (g) time to peak amplitude of Ca²⁺ transients, (h) decay time constant and (i) mean SR Ca²⁺ content in cardiomyocytes from αMHC-Angptl2 Tg (n=54, N=3) and WT littermate mice (n=35, N=3). (j) Relative expression of genes associated with energy metabolism (left), β-fatty acid oxidation (middle) and mitochondrial biogenesis (right) in hearts of 10-week-old αMHC-Angptl2 Tg and WT mice. WT values were set to 1. n=7–9 per group. (k) ATP levels in hearts of 6- and 12-week-old αMHC-Angptl2 Tg and WT mice. n=7-9 per group for 6-week-old mice, n=11 per group for 12-week-old mice. Data are means±s.e.m. Statistical significance was determined by Student’s t test. *P<0.05, **P<0.01, ^†P<0.001 between genotypes. N, number of independent experiments.