DataVXAdvanced SciencePaper
journal article·2023-06Open access

HIPK1 Inhibition Protects against Pathological Cardiac Hypertrophy by Inhibiting the CREB‐C/EBPβ Axis

Yihua Bei, Yujiao Zhu, Meng Wei, Mingming Yin, Lin Li, Chen Chen, Zhenzhen Huang, Xuchun Liang, Juan Gao, Jianhua Yao, Petra H. van der Kraak, Aryan Vink, Zhiyong Lei, Yuxiang Dai, Huihua Chen, Yueyang Liang, Joost PG Sluijter, Junjie Xiao

Advanced Science· Volume 10· Issue 18
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Source abstract

Abstract

Abstract Inhibition of pathological cardiac hypertrophy is recognized as an important therapeutic strategy for heart failure, although effective targets are still lacking in clinical practice. Homeodomain interacting protein kinase 1 (HIPK1) is a conserved serine/threonine kinase that can respond to different stress signals, however, whether and how HIPK1 regulates myocardial function is not reported. Here, it is observed that HIPK1 is increased during pathological cardiac hypertrophy. Both genetic ablation and gene therapy targeting HIPK1 are protective against pathological hypertrophy and heart failure in vivo. Hypertrophic stress‐induced HIPK1 is present in the nucleus of cardiomyocytes, while HIPK1 inhibition prevents phenylephrine‐induced cardiomyocyte hypertrophy through inhibiting cAMP‐response element binding protein (CREB) phosphorylation at Ser271 and inactivating CCAAT/enhancer‐binding protein β (C/EBPβ)‐mediated transcription of pathological response genes. Inhibition of HIPK1 and CREB forms a synergistic pathway in preventing pathological cardiac hypertrophy. In conclusion, HIPK1 inhibition may serve as a promising novel therapeutic strategy to attenuate pathological cardiac hypertrophy and heart failure.
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Research context

OpenAlex topics: Signaling Pathways in Disease · Cardiac Fibrosis and Remodeling · Cardiomyopathy and Myosin Studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Geriatrics (Shanghai University) Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) School of Medicine Shanghai University Nantong 226011 China

Cardiac Regeneration and Ageing Lab Institute of Cardiovascular Sciences Shanghai Engineering Research Center of Organ Repair School of Life Science Shanghai University Shanghai 200444 China

Department of Cardiology Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai 200072 China

Department of Cardiology Shigatse People's Hospital Tibet 857000 China

Department of Pathology University Medical Center Utrecht University Utrecht Utrecht 3584 CX The Netherlands

Department of Cardiology Laboratory of Experimental Cardiology University Medical Center Utrecht University Utrecht Utrecht 3584 CX The Netherlands

Division Lab Central Diagnosis Laboratory Research University Medical Center Utrecht University Utrecht Utrecht 3584 CX The Netherlands

Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai 200032 China

School of Basic Medical Science Shanghai University of Traditional Chinese Medicine Shanghai 201203 China

UMC Utrecht Regenerative Medicine Center University Medical Center Utrecht Utrecht 3508 GA The Netherlands

Funding

National Natural Science Foundation of China · Natural Science Foundation of Shanghai · Natural Science Foundation of Tibet Autonomous Region

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