Downregulation of circ-ZNF609 Promotes Heart Repair by Modulating RNA N6-Methyladenosine-Modified Yap Expression
Knockdown of circ-ZNF609 attenuates LV dysfunction after I/R remodeling in vivo. (a) The schedule of virus injection and myocardial I/R injury-induced mouse pathological cardiac remodeling model establishment. (b) qRT-PCR showed circ-ZNF609 knockdown in mouse hearts via tail-vein injection with AAV9-sh-circ-ZNF609 (, 8, 7, and 10 mice, respectively). (c) Preserved left ventricular ejection fraction (EF) and fractional shortening (FS) in I/R remodeling for 4 weeks of hearts from mice treated with AAV9-sh-circ-ZNF609, as evidenced by echocardiography (, 8, 7, and 10 mice, respectively). (d) Representative images of H&E staining (top, scale μm) and WGA staining (bottom, scale μm). (e) Quantitative analysis of cross-sectional area of cardiac cells stained with WGA at indicated groups ( mice/group). (f) Reduced cardiac fibrosis in I/R remodeling for 4 weeks of hearts from mice treated with AAV9-sh-circ-ZNF609, as evidenced by Masson’s staining ( mice/group, scale μm). (g) Decreased expression of both the pathological hypertrophic genes (Anp, Bnp) and fibrotic genes (α-Sma, Ctgf, Col1a1, and Col3a1) in I/R remodeling for 4 weeks of hearts from mice treated with AAV9-sh-circ-ZNF609 ( mice/group). LV: left ventricular; I/R: ischemia/reperfusion; H&E: hematoxylin-eosin; WGA: wheat germ agglutinin. Data are presented as (b, c, e–g) Two-way ANOVA test.