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DYRK1B-STAT3 Drives Cardiac Hypertrophy and Heart Failure by Impairing Mitochondrial Bioenergetics
Lingfang Zhuang1,2, Kangni Jia1,2, Chen Chen1,3
1Department of Cardiovascular Medicine (L.Z., K..J., Z.L., J.Z., J.H., H.Z., Q.F., C.H., H.X., L.L., W.S., R.Z., K.C., X.Y.), Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Circulation
|March 2, 2022
Summary
Dual-specificity tyrosine-regulated kinase 1B (DYRK1B) promotes heart failure by impairing mitochondrial function. Inhibiting DYRK1B or STAT3 improves cardiac performance and mitochondrial bioenergetics in heart failure models.
Area of Science:
- Cardiology
- Molecular Biology
- Mitochondrial Biology
Background:
- Heart failure is a major global health concern.
- Mitochondrial dysfunction is implicated in heart failure progression, but mechanisms are unclear.
- Kinases can affect mitochondrial function, prompting investigation into DYRK1B.
Purpose of the Study:
- To investigate the role of DYRK1B in mitochondrial bioenergetics, cardiac hypertrophy, and heart failure.
- To elucidate the mechanisms by which DYRK1B influences cardiac function.
Main Methods:
- Engineered DYRK1B transgenic and knockout mice.
- Utilized transverse aortic constriction for in vivo cardiac hypertrophy model.
- Performed RNA-sequencing and mitochondrial functional analyses.
Main Results:
- DYRK1B was upregulated in failing human and hypertrophic murine hearts.
- Overexpression of DYRK1B caused cardiac dysfunction and fibrosis.
- DYRK1B deletion mitigated cardiac hypertrophy and failure by restoring mitochondrial bioenergetics via STAT3/PGC-1α pathway.
Conclusions:
- DYRK1B plays a critical role in mitochondrial dysfunction, cardiac hypertrophy, and heart failure.
- DYRK1B inhibition offers a potential therapeutic strategy for heart failure.
- Targeting DYRK1B or STAT3 can improve cardiac performance by rejuvenating mitochondrial function.
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