Journal: JACC: Basic to Translational Science

Article Title: Loss of YTHDF2 Alters the Expression of m 6 A-Modified Myzap and Causes Adverse Cardiac Remodeling

doi: 10.1016/j.jacbts.2023.03.012

Figure Lengend Snippet: Loss of YTHDF2 Causes Cardiac Dysfunction and Fibrosis (A) Fractional shortening (%) by echocardiography of the littermate control animals and Y2-cKO mice. (B) M-mode echocardiographic measurement of interventricular septal thickness in diastole (IVS,d) as a marker of left ventricular anterior wall thickness. (C) Quantification of fibrosis by Picrosirius red stain. (D) Representative images for Picrosirius red stain of heart cross-sections (fibrosis [red] ). Scale bar = 1,000 μm for the full-sized images and 250 μm for the callouts. (E to G) Electrocardiography parameters recorded during baseline monitoring of the littermate controls and Y2-cKO mice. The values represent means calculated using LabChart Pro ECG Analysis throughout the 5-minute period of recording: (E) heart rates (beats/min), (F) QRS intervals (seconds), and (G) QTc intervals (seconds) adjusted to heart rates. (H, I) Results of the electrocardiogram (ECG) monitoring 15 minutes after epinephrine and caffeine injections. (H) Percent of mice of each genotype which developed either no events or ventricular arrhythmic events in order of increasing event severity (y-axis): isolated premature ventricular contractions (PVCs), frequent PVCs, bigeminy, or ventricular tachycardia. (I) Assigned worst arrhythmia scores to each mouse were based on the worst ventricular arrhythmia displayed and adapted from van der Werf et al : 0 = no events; 1 = isolated PVCs (<10 per minute); 2 = frequent PVCs (≥10 per minute); 3 = ventricular bigeminy; 4 = ventricular tachycardia. Normally distributed data were compared using the unpaired 2-tailed t test with Welch's correction for unequal variances or Wilcoxon rank sum test for skewed data: ∗ P ≤ 0.05, ∗∗ P ≤ 0.01, ∗∗∗ P ≤ 0.001. Incidence of arrhythmic events in the 2 groups was compared by Fisher exact test. Data are presented as the mean ± SEM with the individual data points shown. Group sizes are listed in order of control and Y2-cKO mice: (A, B) n = 18, 10; (C) n = 11, 6; (E to G) n = 11, 13: (I) n = 7, 13. Abbreviations as in Figure 1 .

Article Snippet: The baseline recording was performed for 5 minutes, and the standard parameters (heart rates; P duration; PR, QRS, QT, JT, QTc, JTc, and RR intervals; ST height; and all wave amplitudes) were calculated using LabChart Pro ECG Analysis v2.3.2 module (ADInstruments).

Techniques: Marker, Staining, Isolation