Related Experiment Video

Updated: Oct 24, 2025

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
10:21

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix

Published on: June 14, 2016

10.3K

Serum circulating proteins from pediatric patients with dilated cardiomyopathy cause pathologic remodeling and

Danielle A Jeffrey1, Julie Pires Da Silva1, Anastacia M Garcia2

  • 1Department of Medicine and.

JCI Insight
|August 12, 2021
PubMed

Insights

Serum proteins, not miRNAs, drive pediatric dilated cardiomyopathy (DCM) by activating the fetal gene program and increasing heart cell stiffness. This research identifies key proteins like MDK and sFRP1, offering new therapeutic targets for pediatric DCM.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Pediatric Research

Background:

  • Dilated cardiomyopathy (DCM) is a leading cause of heart failure and transplantation in children.
  • Current pediatric DCM therapies are limited by a lack of effective disease models.
  • Previous studies indicated serum from DCM patients activates the fetal gene program (FGP) in neonatal rat ventricular myocytes (NRVMs).

Purpose of the Study:

  • To investigate the role of circulating factors in pediatric DCM pathogenesis.
  • To identify specific serum components responsible for pathological changes in heart cells.
  • To explore potential therapeutic targets for pediatric DCM.

Main Methods:

  • NRVMs were treated with serum from pediatric DCM patients.
  • Proteinase K and RNase treatments were used to differentiate the effects of proteins and miRNAs.
  • Secretome analysis, RNA-sequencing, and Atomic Force Microscopy were employed to assess molecular and cellular changes.
  • Specific protein treatments (MDK, sFRP1) were used to validate findings.

Main Results:

  • Serum proteins, not miRNAs, were identified as drivers of FGP activation in NRVMs.
  • Midkine (MDK) was upregulated in DCM serum and induced FGP activation.
  • Extracellular matrix remodeling and focal adhesion pathways were upregulated, correlating with increased cellular stiffness.
  • Secreted frizzled-related protein 1 (sFRP1) was implicated in increasing cellular stiffness.

Conclusions:

  • Circulating serum proteins promote pathological gene expression and cellular stiffness in pediatric DCM.
  • Midkine (MDK) and secreted frizzled-related protein 1 (sFRP1) are key proteins involved in DCM pathogenesis.
  • Circulating miRNAs appear to have a protective role against DCM-related pathological changes.

Keywords:
CardiologyCardiovascular diseaseMolecular biology

More Related Videos

In Vitro Assessment of Cardiac Function Using Skinned Cardiomyocytes08:19

In Vitro Assessment of Cardiac Function Using Skinned Cardiomyocytes

Published on: June 22, 2020

6.7K
Sarcomere Shortening of Pluripotent Stem Cell-Derived Cardiomyocytes using Fluorescent-Tagged Sarcomere Proteins.08:37

Sarcomere Shortening of Pluripotent Stem Cell-Derived Cardiomyocytes using Fluorescent-Tagged Sarcomere Proteins.

Published on: March 3, 2021

4.7K

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,...
86
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...
126
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...
100
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...
136
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...
108
Cardiomyopathy V: Interprofessional Care01:29

Cardiomyopathy V: Interprofessional Care

Managing cardiomyopathy involves addressing underlying or precipitating causes, treating heart failure with medications, and implementing dietary changes and a balanced exercise and rest regimen.Lifestyle ModificationsCardiomyopathy patients should adopt a low-sodium diet to reduce fluid retention and manage heart failure. A personalized exercise and rest plan helps maintain physical fitness without overstraining the heart. Avoiding alcohol and tobacco is essential to prevent further damage to...
73