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Ovarian Tumor Domain-Containing 7B Attenuates Pathological Cardiac Hypertrophy by Inhibiting Ubiquitination and

Bin-Bin Du1, Jie-Lei Zhang2, Ling-Yao Kong1

  • 1Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.

Journal of the American Heart Association
|December 12, 2023
PubMed

Insights

Ovarian tumor domain-containing 7B (OTUD7B) protein deficiency worsens cardiac hypertrophy. Targeting the OTUD7B-KLF4 pathway may offer new treatments for this heart condition.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Cardiac hypertrophy (CH) is a major risk factor for cardiovascular diseases and mortality, particularly in older adults.
  • Current pharmacological treatments for CH are limited.
  • The role of ovarian tumor domain-containing 7B (OTUD7B) in CH development is not well understood.

Purpose of the Study:

  • To investigate the role of OTUD7B in the development of cardiac hypertrophy.
  • To explore the potential of the OTUD7B-KLF4 axis as a therapeutic target for CH.

Main Methods:

  • Utilized OTUD7B knockout mice undergoing transverse aortic coarctation surgery.
  • Assayed OTUD7B function in isolated neonatal rat cardiomyocytes.
  • Performed immunoprecipitation-mass spectrometry to identify binding partners of OTUD7B.

Main Results:

  • OTUD7B expression was reduced in hypertrophic hearts and cardiomyocytes.
  • OTUD7B deficiency aggravated CH, cardiac dysfunction, and fibrosis in mice.
  • OTUD7B directly binds to KLF4, inhibiting its ubiquitination and degradation, thereby suppressing myocardial hypertrophy.

Conclusions:

  • The OTUD7B-KLF4 axis plays a critical role in regulating cardiac hypertrophy.
  • This axis represents a novel molecular target for the development of CH treatments.
Abstract

Keywords:
AKT signaling pathwayKLF4cardiac hypertrophyovarian tumor domain‐containing 7B

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