Ovid Technologies (Wolters Kluwer Health)

Circulation

, volume 145 , issue 11 , pages 829-846

DYRK1B-STAT3 Drives Cardiac Hypertrophy and Heart Failure by Impairing Mitochondrial Bioenergetics

Lingfang Zhuang ^{1, 2}

Kangni Jia ^{1, 2}

Chen Chen ^{1, 3}

Zhigang Li ^{1, 2}

Jiaxin Zhao ^{1, 4}

Jian Hu ^{1, 4}

Zhang Hang ^{1, 4}

QIN FAN ^{1, 2}

Chunkai Huang ^{1, 4}

Hongyang Xie ^{1, 2}

Lin LÜ ^{1, 2}

WEIFENG SHEN ^{1, 2}

Guang Ning ^{1, 4}

Jiqiu Wang ^{1, 4}

Ruiyan Zhang ^{1, 4}

Chen Kang ¹

Xiaoxiang Yan ^{1, 2}

Hide authors affiliations Show authors affiliations: 4 affiliations

Department 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. |

Ruijin Hospital, Institute of Cardiovascular Diseases (L.Z., K..J., Z.L., J.Z., J.H., H.Z., Q.F., C.H., H.X., L.L., W.S., R.Z., X.Y.), Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. |

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (C.C.). |

⁴

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases (G.N., J.W.), Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. |

Publication type: Journal Article

Publication date: 2022-03-02

Ovid Technologies (Wolters Kluwer Health)

Circulation

scimago Q1

wos Q1

SJR: 8.668

CiteScore: 45.1

Impact factor: 38.6

ISSN: 00097322, 15244539

DOI: 10.1161/circulationaha.121.055727

Copy DOI

PubMed ID: 35235343

Cardiology and Cardiovascular Medicine

Physiology (medical)

Abstract

Background:

Heart failure is a global public health issue that is associated with increasing morbidity and mortality. Previous studies have suggested that mitochondrial dysfunction plays critical roles in the progression of heart failure; however, the underlying mechanisms remain unclear. Because kinases have been reported to modulate mitochondrial function, we investigated the effects of DYRK1B (dual-specificity tyrosine-regulated kinase 1B) on mitochondrial bioenergetics, cardiac hypertrophy, and heart failure.

Methods:

We engineered DYRK1B transgenic and knockout mice and used transverse aortic constriction to produce an in vivo model of cardiac hypertrophy. The effects of DYRK1B and its downstream mediators were subsequently elucidated using RNA-sequencing analysis and mitochondrial functional analysis.

Results:

We found that DYRK1B expression was clearly upregulated in failing human myocardium and in hypertrophic murine hearts, as well. Cardiac-specific DYRK1B overexpression resulted in cardiac dysfunction accompanied by a decline in the left ventricular ejection fraction, fraction shortening, and increased cardiac fibrosis. In striking contrast to DYRK1B overexpression, the deletion of DYRK1B mitigated transverse aortic constriction–induced cardiac hypertrophy and heart failure. Mechanistically, DYRK1B was positively associated with impaired mitochondrial bioenergetics by directly binding with STAT3 to increase its phosphorylation and nuclear accumulation, ultimately contributing toward the downregulation of PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α). Furthermore, the inhibition of DYRK1B or STAT3 activity using specific inhibitors was able to restore cardiac performance by rejuvenating mitochondrial bioenergetics.

Conclusions:

Taken together, the findings of this study provide new insights into the previously unrecognized role of DYRK1B in mitochondrial bioenergetics and the progression of cardiac hypertrophy and heart failure. Consequently, these findings may provide new therapeutic options for patients with heart failure.

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GOST Copy

Zhuang L. et al. DYRK1B-STAT3 Drives Cardiac Hypertrophy and Heart Failure by Impairing Mitochondrial Bioenergetics // Circulation. 2022. Vol. 145. No. 11. pp. 829-846.

GOST all authors (up to 50) Copy

Zhuang L., Jia K., Chen C., Li Z., Zhao J., Hu J., Hang Z., FAN Q., Huang C., Xie H., LÜ L., SHEN W., Ning G., Wang J., Zhang R., Kang C., Yan X. DYRK1B-STAT3 Drives Cardiac Hypertrophy and Heart Failure by Impairing Mitochondrial Bioenergetics // Circulation. 2022. Vol. 145. No. 11. pp. 829-846.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1161/circulationaha.121.055727

UR - https://doi.org/10.1161/circulationaha.121.055727

TI - DYRK1B-STAT3 Drives Cardiac Hypertrophy and Heart Failure by Impairing Mitochondrial Bioenergetics

T2 - Circulation

AU - Zhuang, Lingfang

AU - Jia, Kangni

AU - Chen, Chen

AU - Li, Zhigang

AU - Zhao, Jiaxin

AU - Hu, Jian

AU - Hang, Zhang

AU - FAN, QIN

AU - Huang, Chunkai

AU - Xie, Hongyang

AU - LÜ, Lin

AU - SHEN, WEIFENG

AU - Ning, Guang

AU - Wang, Jiqiu

AU - Zhang, Ruiyan

AU - Kang, Chen

AU - Yan, Xiaoxiang

PY - 2022

DA - 2022/03/02

PB - Ovid Technologies (Wolters Kluwer Health)

SP - 829-846

IS - 11

VL - 145

PMID - 35235343

SN - 0009-7322

SN - 1524-4539

ER -

BibTex |

Cite this

BibTex (up to 50 authors) Copy

@article{2022_Zhuang,

author = {Lingfang Zhuang and Kangni Jia and Chen Chen and Zhigang Li and Jiaxin Zhao and Jian Hu and Zhang Hang and QIN FAN and Chunkai Huang and Hongyang Xie and Lin LÜ and WEIFENG SHEN and Guang Ning and Jiqiu Wang and Ruiyan Zhang and Chen Kang and Xiaoxiang Yan},

title = {DYRK1B-STAT3 Drives Cardiac Hypertrophy and Heart Failure by Impairing Mitochondrial Bioenergetics},

journal = {Circulation},

year = {2022},

volume = {145},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

month = {mar},

url = {https://doi.org/10.1161/circulationaha.121.055727},

number = {11},

pages = {829--846},

doi = {10.1161/circulationaha.121.055727}

}

MLA

Cite this

MLA Copy

Zhuang, Lingfang, et al. “DYRK1B-STAT3 Drives Cardiac Hypertrophy and Heart Failure by Impairing Mitochondrial Bioenergetics.” Circulation, vol. 145, no. 11, Mar. 2022, pp. 829-846. https://doi.org/10.1161/circulationaha.121.055727.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Journal

Circulation

scimago Q1

wos Q1

SJR

8.668

CiteScore

45.1

Impact factor

38.6

ISSN

00097322 (Print)

15244539 (Electronic)