fig1

Figure 1. HIF2A is necessary for hypoxia-mediated cardiomyocyte proliferation. (A) qPCR for HIF1A and HIF2A in control and MCM;HIF1A^f/f or HIF2A^f/f mice, respectively, in normoxia. (B) Quantification of pH3+ cardiomyocytes in hypoxia-exposed control, Myh6-MCM;HIF1A^f/f, and Myh6-MCM;HIF2A^f/f mice. (C) Representative image of pH3-labeled cardiomyocyte nucleus (white arrow) in Myh6-MCM;HIF2A^f/f. (Scale bar 10 µm). (D) TUNEL staining quantification in the hearts of control, Myh6-MCM;HIF1A^f/f, and Myh6-MCM;HIF2A^f/f mice placed in chronic hypoxia. (E) Genetic model used for HIF2A-OE experiments. (F) qPCR for human HIF2A in control and MCM;HIF2A-OE hearts, relative to 18 S. (G) Heart weight-body weight ratio (mg/g) of control and MCM;HIF2A-OE mice. (H-I) Cardiac function assessed by EF and FS of control and MCM;HIF2A-OE mice. (J) Average cardiomyocyte cell size determined by WGA quantification of control and MCM;HIF2A-OE mice. (K) Mean number of isolated cardiomyocytes digested from control and MCM;HIF2A-OE hearts. (L) Representative cell pellets derived upon digestion of control and MCM;HIF2A-OE hearts. pH3: Phosphorylated histone H3; EF: ejection fraction; FS: fractional shortening; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; OE: overexpression; WGA: wheat germ agglutinin. Each dot represents one biological replicate.