Inhibition of SLC26A4 ameliorates cardiac hypertrophy by regulating cardiomyocyte apoptosis and autophagy

ObjectiveTo investigate whether inhibiting SLC26A4 can improve myocardial hypertrophy by reducing cardiomyocyte apoptosis and autophagy.MethodsH9C2 cells were divided into control, PE, NC, PE+NC, PE+SiRNA-SLC26A4, and SiRNASLC26A4 groups. Partial cells were treated with 200 μmol·L-1 PE to induce hypertrophy and transfected with adenovirus vectors carrying NC or SLC26A4 siRNA. Immunofluorescence was used to detect α -SMA, RT-qPCR to measure mRNA levels of SLC26A4, ANP, BNP, and GSK-3β, Western blot to analyze Bcl-2, Bax, Caspase-3, p53, Beclin-1, LC3, and p62 proteins, and flow cytometry to assess apoptosis rates. Concurrently, an aortic coarctation(AAC) -induced myocardial hypertrophy rat model was established, divided into control, hypertrophy, and siRNASLC26A4 groups, with the latter receiving siRNASLC26A4 injection. Cell size was assessed via HE staining, while RT-qPCR and Western blot analyzed corresponding molecular expression.ResultsCompared with the control group, the PE group exhibited increased relative cell area and SLC26A4 mRNA expression. Compared with the NC group, the siRNASLC26A4 group showed decreased relative cell area and reduced SLC26A4, ANP, and BNP mRNA expression, whereas the PE+NC group demonstrated increased levels of these indicators. Compared with the PE+NC group, the PE+siRNA-SLC26A4 group exhibited decreased levels of all indicators. Regarding apoptosis, the apoptosis rate was higher in the siRNASLC26A4 group than in the NC group, lower in the PE+NC group than in the NC group, and higher in the PE+siRNA-SLC26A4 group than in the PE+NC group. Autophagy-related markers showed that LC3 Ⅱ/Ⅰ and Beclin-1 expression was higher in the siRNASLC26A4 group than in the NC group, while p62 expression was reduced. In the PE+siRNA-SLC26A4 group, LC3Ⅱ/Ⅰ and Beclin-1 expression was lower than in the PE+NC group, and p62 expression increased. Serum GSK-3β levels were lower in the hypertrophic group than in the control group, while the siRNA-SLC26A4 group showed higher levels than the hypertrophic group. Additionally, the Bcl-2/Bax ratio was lower in the hypertrophic cardiomyopathy group than in the control group, while p53 and Caspase-3 expression increased. The Bcl-2/Bax ratio was higher in the siRNA-SLC26A4 group than in the hypertrophic cardiomyopathy group, with decreased p53 and Caspase-3 expression. The hypertrophic group showed higher LC3 Ⅱ/Ⅰ and Beclin-1 expression than the control group, with decreased p62 expression; the siRNA-SLC26A4 group exhibited lower LC3 Ⅱ/Ⅰ Beclin-1 expression than the hypertrophic group, with upregulation of p62 expression.ConclusionInhibition of SLC26A4 improves myocardial hypertrophy by regulating cardiomyocyte apoptosis and autophagy.