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Updated: Dec 29, 2025
Isolation of Atrial Cardiomyocytes from a Rat Model of Metabolic Syndrome-related Heart Failure with Preserved Ejection Fraction
Published on: July 26, 2018
Inhibiting SLC26A4 reverses cardiac hypertrophy in H9C2 cells and in rats
Liqun Tang1, Xiaoqin Yu2, Yangyang Zheng1
1Department of Geriatrics, Zhejiang Province People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Background:
It has been confirmed that mutations in solute carrier family 26 member 4 (SLC26A4) contribute to pendred syndrome. However, the role of SLC26A4 in cardiac hypertrophy and the signaling pathways remain unclear.
Methods:
Cardiomyocytes were treated by 200 µM phenylephrine (PE) to induce cardiac hypertrophy. Also, the expression of SLC26A4, GSK3, cardiac hypertrophy markers including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was detected through real-time quantitative polymerase chain reaction (RT-qPCR). Flow cytometry assay was used to test the apoptosis of PE-induced cardiomyocytes transfected by small interfere RNA (siRNA)-SLC26A4. Furthermore, we detected the expression of autophagy-related markers including light chain 3 (LC3) and P62. Finally, we established a rat model of abdominal aortic constriction (AAC)-induced cardiac hypertrophy in vivo.
Results:
RT-qPCR results showed that the mRNA expression of SLC26A4 was significantly up-regulated in PE-induced cardiac hypertrophy. After inhibiting SLC26A4, the release of ANP and BNP was significantly decreased and GSK3β was elevated in vivo and in vitro. Furthermore, inhibiting SLC26A4 promoted apoptosis of cardiac hypertrophy cells. In addition, LC3 was down-regulated and P62 was enhanced after transfection of siRNA-SLC26A4.
Conclusion:
Our findings revealed that SLC26A4 increases cardiac hypertrophy, and inhibiting SLC26A4 could decrease the release of ANP/BNP and promote the expression of GSK-3β in vitro and in vivo. Moreover, SLC26A4 silencing inhibits autophagy of cardiomyocytes and induces apoptosis of cardiomyocytes. Therefore, SLC26A4 possesses potential value to be a therapeutic target of cardiac hypertrophy, and our study provides new insights into the mechanisms of cardiac hypertrophy.
Insights
Solute carrier family 26 member 4 (SLC26A4) promotes cardiac hypertrophy by inhibiting autophagy and inducing apoptosis. Inhibiting SLC26A4 decreases cardiac hypertrophy markers and increases GSK-3β expression, suggesting SLC26A4 as a therapeutic target.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Mutations in solute carrier family 26 member 4 (SLC26A4) are linked to Pendred syndrome.
- The specific role of SLC26A4 in cardiac hypertrophy and its associated signaling pathways remain largely uncharacterized.
Purpose of the Study:
- To investigate the role of SLC26A4 in the development of cardiac hypertrophy.
- To elucidate the underlying molecular mechanisms and signaling pathways involved in SLC26A4-mediated cardiac hypertrophy.
Main Methods:
- Cardiac hypertrophy was induced in vitro using phenylephrine (PE) and in vivo using abdominal aortic constriction (AAC) in a rat model.
- Expression levels of SLC26A4, GSK3, and cardiac hypertrophy markers (ANP, BNP) were quantified using RT-qPCR.
- Apoptosis and autophagy markers (LC3, P62) were assessed in PE-induced cardiomyocytes following SLC26A4 inhibition via siRNA.
Main Results:
- SLC26A4 mRNA expression was significantly upregulated in PE-induced cardiac hypertrophy.
- Inhibition of SLC26A4 led to decreased ANP and BNP release and elevated GSK3β expression both in vitro and in vivo.
- Silencing SLC26A4 promoted cardiomyocyte apoptosis and inhibited autophagy, evidenced by reduced LC3 and increased P62 levels.
Conclusions:
- SLC26A4 plays a significant role in promoting cardiac hypertrophy.
- Inhibiting SLC26A4 demonstrates therapeutic potential by reducing hypertrophy markers and modulating GSK-3β, autophagy, and apoptosis pathways.
- SLC26A4 represents a promising therapeutic target for cardiac hypertrophy, offering new mechanistic insights into the disease.
