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The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
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Updated: May 23, 2025

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Asb10 accelerates pathological cardiac remodeling by stabilizing HSP70.

Ke Lin1,2,3, Wenjie Wei2,4, Songzan Chen1,2,3

  • 1Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

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Summary

Asb10 exacerbates cardiac hypertrophy by stabilizing HSP70, a key factor in heart failure development. Inhibiting Asb10 may offer a therapeutic strategy for pressure overload-induced heart conditions.

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Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Heart Failure Pathogenesis

Background:

  • Cardiac hypertrophy is a major risk factor for heart failure.
  • Hypertension-induced pressure overload is a common trigger for left ventricular hypertrophy.
  • The ubiquitin-proteasome system's role in cardiac hypertrophy is increasingly recognized.

Purpose of the Study:

  • To investigate the role of Asb10, a heart tissue-enriched E3 ligase, in cardiac hypertrophy and heart failure.
  • To elucidate the molecular mechanisms by which Asb10 influences cardiac hypertrophy.

Main Methods:

  • Bioinformatic screening of GEO datasets and experimental validation.
  • In vitro studies using NRVMs with adenoviral Asb10 overexpression.
  • Immunoprecipitation-mass spectrometry and co-immunoprecipitation assays.
  • In vivo studies in mice subjected to Transverse Aortic Constriction (TAC) surgery.

Main Results:

  • Asb10 was identified as downregulated in cardiac hypertrophy.
  • Asb10 overexpression exacerbated hypertrophic growth and worsened cardiac function post-TAC.
  • Asb10 stabilizes HSP70 by blocking STUB1-mediated ubiquitination and degradation.
  • Elevated HSP70, cardiac inflammation, and pHDAC2S394 activation were linked to Asb10's effects.

Conclusions:

  • Asb10 exacerbates cardiac hypertrophy by stabilizing HSP70 through competitive inhibition of STUB1.
  • Asb10 plays a significant role in hemodynamic stress-induced cardiac hypertrophy and heart failure.
  • Targeting Asb10 or HSP70 may represent a therapeutic approach for heart failure.