Related Experiment Video

Updated: Oct 3, 2025

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
08:09

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

Published on: June 7, 2018

9.9K

Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathy

Yingchao Shi1, Wenli Fan1, Mingjie Xu1

  • 1State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, and Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, China.

JCI Insight
|February 15, 2022
PubMed

Insights

Znhit1 is essential for maintaining heart function by regulating calcium (Ca2+) homeostasis. Its absence leads to severe cardiac issues, including arrhythmia and heart failure, primarily due to altered Casq1 levels.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Epigenetics

Background:

  • Cardiac calcium (Ca2+) homeostasis is vital for heart function, and disruptions cause heart failure and arrhythmia.
  • Chromatin remodeling influences cardiac gene expression, but its role in Ca2+ regulation is unclear.

Purpose of the Study:

  • To investigate the role of Znhit1, a component of the SRCAP chromatin remodeling complex, in cardiac Ca2+ homeostasis and heart function.

Main Methods:

  • Utilized a mouse model with Znhit1 deletion in postnatal hearts.
  • Analyzed cardiac function, Ca2+ handling proteins (Casq1, SERCA2a), and epigenetic modifications (H2A.Z deposition).
  • Generated Znhit1 Casq1 double knockout mice to assess Casq1's role.

Main Results:

  • Znhit1 deletion caused arrhythmia, vacuolar cardiomyopathy, heart failure, and sudden death in mice.
  • Absence of Znhit1 led to increased Casq1 and decreased SERCA2a protein levels.
  • Znhit1 regulated Casq1 and SERCA2a expression via H2A.Z deposition at their promoters.
  • Deleting Casq1 ameliorated vacuolar formation in Znhit1-deficient hearts.

Conclusions:

  • Znhit1 is crucial for postnatal heart function and cardiac Ca2+ homeostasis.
  • Znhit1-dependent regulation of Casq1 and SERCA2a is essential for preventing cardiomyopathy.
  • Accumulation of Casq1 is implicated as a causative factor in Znhit1-associated vacuolar cardiomyopathy.

Keywords:
CalciumCardiologyCardiovascular diseaseHeart failure

More Related Videos

Light-sheet Fluorescence Microscopy to Capture 4-Dimensional Images of the Effects of Modulating Shear Stress on the Developing Zebrafish Heart06:51

Light-sheet Fluorescence Microscopy to Capture 4-Dimensional Images of the Effects of Modulating Shear Stress on the Developing Zebrafish Heart

Published on: August 10, 2018

8.5K
Immunostaining of Dissected Zebrafish Embryonic Heart06:23

Immunostaining of Dissected Zebrafish Embryonic Heart

Published on: January 10, 2012

17.9K

Related Concept Videos

Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
78
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
77
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
50