Cardiac hypertrophy in anion exchanger 1-null mutant mice with severe hemolytic anemia

Anion exchanger 1 (AE1; SLC4A1), the plasma membrane Cl−/HCO3− exchanger of erythrocytes, is also expressed in heart. The aim of this study was to assess the role of AE1 in heart function through study of AE1-null (AE1−/−) mice, which manifest severe hemolytic anemia resulting from erythrocyte fragility. Heart weight-to-body weight ratios were significantly higher in the AE1−/− mice than in wild-type (AE1+/+) littermates at both 1–3 days postnatal (3.01 ± 0.38 vs. 1.45 ± 0.04) and at 7 days postnatal (9.45 ± 0.53 vs. 4.13 ± 0.41), indicating that loss of AE1 led to cardiac hypertrophy. Heterozygous (AE1+/−) mice had no signs of cardiac hypertrophy. Morphology of the adult AE1−/− mutant heart revealed an increased left ventricular mass, accompanied by increased collagen deposition and fibrosis. M-mode echocardiography revealed dysfunction of the AE1−/− hearts, including dilated left ventricle end diastole and systole and expanded left ventricular mass compared with AE1+/+ hearts. Expression of intracellula...