Related Experiment Video

Updated: Sep 20, 2026

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
09:36

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia

Published on: December 22, 2023

Disruption of cardiac Ena-VASP protein localization in intercalated disks causes dilated cardiomyopathy

Martin Eigenthaler1, Stefan Engelhardt, Birgitta Schinke

  • 1Institut für Klinische Biochemie und Pathobiochemie, Universität Würzburg, Germany.

American Journal of Physiology. Heart and Circulatory Physiology
|August 23, 2003
PubMed

Insights

Ena-VASP proteins are crucial for heart function. Inhibiting them with the VASP-EVH1 domain in mice caused dilated cardiomyopathy and early death, highlighting their role in cardiac intercalated disks.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cell Biology
  • Biochemistry

Background:

  • Vasodilator-stimulated phosphoprotein (VASP) and mammalian enabled (Mena) are key regulators of the actin cytoskeleton and signaling pathways.
  • Ena-VASP proteins, characterized by their EVH1 domain, interact with partners like zyxin and vinculin.
  • While VASP and Mena are abundant in the heart, their specific roles were unclear from single-gene knockout studies.

Purpose of the Study:

  • To investigate the in vivo function of Ena-VASP proteins in the heart.
  • To elucidate the role of Ena-VASP proteins in cardiac intercalated disk function.

Main Methods:

  • Generation of transgenic mice with cardiac-specific expression of the VASP-EVH1 domain using the alpha-myosin heavy chain promoter.
  • Utilizing a dominant-negative strategy to displace endogenous VASP and Mena proteins from cardiac structures.
  • Analysis of cardiac phenotype, including myocyte structure, heart rate, and survival.

Main Results:

  • Cardiac-specific overexpression of the VASP-EVH1 domain successfully displaced VASP and Mena from intercalated disks.
  • Transgenic mice developed dilated cardiomyopathy, characterized by myocyte hypertrophy and bradycardia.
  • High levels of transgene expression led to early postnatal lethality in affected mice.

Conclusions:

  • Ena-VASP proteins are essential for maintaining normal cardiac structure and function.
  • These proteins play a critical role in the integrity and function of cardiac intercalated disks.
  • Disruption of Ena-VASP function leads to severe cardiac pathology and reduced survival.

More Related Videos

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo05:14

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

Published on: May 16, 2020

Related Concept Videos

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,...
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...
Myocarditis I: Introduction01:21

Myocarditis I: Introduction

Myocarditis is inflammation of the myocardium, which is the muscular layer of the heart.EtiologyMyocarditis has a diverse etiology, including a wide range of infectious and non-infectious causes:Infectious CausesViral: Common viruses include Coxsackie A and B, adenovirus, parvovirus B19, enteroviruses, and influenza A.Bacterial: Examples include infections caused by Streptococcus, Staphylococcus, and Mycoplasma species.Rickettsial: Infections like Rocky Mountain spotted fever can result in...
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...
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...
Mitral Valve Prolapse I: Introduction01:27

Mitral Valve Prolapse I: Introduction

IntroductionThe mitral valve, one of the heart's four valves, regulates blood flow. These valves have flaps that open and close to direct blood properly through the heart and body. During each heartbeat, the flaps open for blood to pass through and seal shut to prevent backflow. Specifically, the mitral valve opens to allow blood flow from the heart's upper left chamber to the lower left chamber. It then closes securely as the lower left chamber contracts to pump blood to the body, preventing...