Related Experiment Video

Updated: Feb 27, 2026

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse
10:22

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

Published on: October 26, 2017

22.9K

Increased Postnatal Cardiac Hyperplasia Precedes Cardiomyocyte Hypertrophy in a Model of Hypertrophic Cardiomyopathy

Emily T Farrell1, Adrian C Grimes2, Willem J de Lange1

  • 1Department of Pediatrics, University of Wisconsin School of Medicine and Public HealthMadison, WI, United States.

Frontiers in Physiology
|June 30, 2017
PubMed

Insights

In hypertrophic cardiomyopathy (HCM), increased cell division, not just cell growth, precedes heart enlargement in a mouse model. This early proliferation may determine disease severity in this common genetic heart condition.

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Genetics

Background:

  • Hypertrophic cardiomyopathy (HCM) affects ~0.5% of the population and is a major cause of sudden cardiac death in young adults.
  • While cardiomyocyte hypertrophy is the accepted mechanism for cardiac enlargement in HCM, the early signaling pathways initiating this process remain poorly understood.
  • Mutations in cardiac myosin binding protein C (MYBPC3) are a common cause of HCM.

Purpose of the Study:

  • To investigate the early cellular and molecular events preceding overt cardiac enlargement in a mouse model of MYBPC3-associated HCM.
  • To characterize the perinatal phenotype of cMyBP-C knockout (cMyBP-C-/-) mice, which rapidly develop cardiomegaly.
  • To determine whether cardiomyocyte proliferation or hypertrophy is the primary driver of early cardiac growth in this model.

Main Methods:

  • Utilized a cMyBP-C-/- mouse model of HCM, comparing knockout mice to wild-type littermates.
  • Employed a multi-omics approach including microarray analysis, quantitative PCR (qPCR), and immunohistochemistry (IHC).
  • Conducted echocardiography and isolated cardiomyocyte measurements to assess cardiac function and cell size/number over a time course from birth to postnatal day 9.

Main Results:

  • cMyBP-C-/- hearts exhibited elevated cardiomyocyte cell cycling at postnatal day 1, preceding the onset of overt hypertrophy by postnatal day 9.
  • Increased heart weight-to-body weight ratios were observed prior to cellular hypertrophy, correlating with increased cardiomyocyte proliferation.
  • Heterozygous cMyBP-C deletion showed a trend towards increased heart size but did not reach statistical significance by postnatal day 9.

Conclusions:

  • Altered cell cycle regulation and elevated cardiomyocyte proliferation precede hypertrophy in the cMyBP-C-/- HCM mouse model.
  • Increased cardiomyocyte number, resulting from proliferation, contributes significantly to early heart enlargement in this HCM model.
  • The pre-hypertrophic period characterized by proliferation represents a critical window for determining HCM commitment and disease severity.

Keywords:
HCMMyBP-Ccell cyclinghyperplasiahypertrophic cardiomyopathymyosin binding protein Cproliferation

More Related Videos

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

4.3K
A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats07:31

A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats

Published on: December 2, 2016

10.7K

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...
568
Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
1.1K
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,...
667
Cardiomyopathy I: Introduction and Classification01:25

Cardiomyopathy I: Introduction and Classification

Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
700