Related Experiment Video

Updated: Jun 19, 2026

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
11:00

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

Published on: September 18, 2017

SORBS2 regulates diastolic function through cytoskeletal networks and calcium handling

Zexuan Wu1, Camille Blandin1, Jiehui Chen1

  • 1Department of Cardiology, Boston Children's Hospital, Boston, MA, USA.

Communications Biology
|June 17, 2026
PubMed

Insights

Genetic ablation of SORBS2 causes diastolic dysfunction in mice, impacting heart relaxation and stiffness. Restoring SORBS2 improves heart function and survival, highlighting its role in regulating cardiac mechanics.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Diastolic dysfunction is key in heart failure with preserved ejection fraction.
  • Mechanisms within cardiomyocytes are not fully understood.
  • SORBS2's role in cardiac function is unclear.

Purpose of the Study:

  • Investigate the role of SORBS2 in cardiomyocyte adhesion complexes.
  • Determine the impact of SORBS2 deficiency on cardiac function and survival.
  • Elucidate the molecular mechanisms by which SORBS2 regulates diastolic function.

Main Methods:

  • Genetic ablation of SORBS2 in mice.
  • Assessment of cardiac structure and function (diastolic and systolic indices).
  • Analysis of cardiomyocyte adhesion complexes, cytoskeletal remodeling, calcium homeostasis, and extracellular matrix remodeling.

Main Results:

  • SORBS2 genetic ablation led to progressive diastolic dysfunction, atrial enlargement, and reduced survival in mice.
  • Postnatal re-expression of SORBS2 rescued diastolic function and improved longevity.
  • SORBS2 deficiency disrupted microtubule organization, reduced SERCA2, impaired calcium handling, and promoted fibrosis.
  • Pharmacological inhibition of microtubule detyrosination partially rescued relaxation defects.

Conclusions:

  • SORBS2 is essential for cardiomyocyte adhesion and regulating diastolic function.
  • SORBS2 acts as a scaffold linking cytoskeletal integrity, calcium homeostasis, and extracellular matrix.
  • Targeting SORBS2 or associated pathways may offer therapeutic strategies for diastolic dysfunction.

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