Related Experiment Video

Updated: Aug 9, 2025

An Approach to Study Shape-Dependent Transcriptomics at a Single Cell Level
06:02

An Approach to Study Shape-Dependent Transcriptomics at a Single Cell Level

Published on: November 2, 2020

5.8K

Multi-Omic Architecture of Obstructive Hypertrophic Cardiomyopathy

Ramin Garmany1,2, J Martijn Bos2,3,4, David J Tester2

  • 1Mayo Clinic Medical Scientist Training Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic Alix School of Medicine, Rochester, MN (R.G.).

Circulation. Genomic and Precision Medicine
|February 21, 2023
PubMed

Insights

Hypertrophic cardiomyopathy involves abnormal heart muscle growth. This study found that while gene expression downregulates key pathways, the heart muscle protein activity (proteome) upregulates them, particularly the RAS-MAPK cascade, suggesting its role in HCM.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Systems Biology

Background:

  • Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease characterized by left ventricular hypertrophy.
  • The precise molecular pathways driving HCM pathogenesis remain incompletely understood.
  • Identifying these pathways is crucial for developing targeted therapies to manage HCM.

Purpose of the Study:

  • To conduct a comprehensive multi-omic analysis of hypertrophy pathways in HCM.
  • To elucidate the molecular mechanisms underlying cardiac hypertrophy in HCM patients.

Main Methods:

  • Collected cardiac tissue samples from 97 HCM patients and 23 controls.
  • Performed RNA sequencing, deep proteomic, and phosphoproteomic analyses.
  • Utilized differential expression, gene set enrichment, and pathway analyses.

Main Results:

  • Identified widespread transcriptional dysregulation with 1246 differentially expressed genes.
  • Revealed downregulation of 10 hypertrophy pathways at the transcriptomic level.
  • Found upregulation of 7 hypertrophy pathways at the proteomic level, primarily involving the RAS-MAPK signaling cascade, with evidence of its activation via hyperphosphorylation.

Conclusions:

  • The ventricular proteome in HCM shows widespread activation of hypertrophy pathways, notably the RAS-MAPK cascade, irrespective of genotype.
  • A counterregulatory transcriptional downregulation of these same pathways was observed.
  • RAS-MAPK pathway activation is implicated as a critical factor in the hypertrophy characteristic of HCM.
Abstract

Keywords:
cardiomyopathygene expression profilinggenotypehumanshypertrophicproteomics

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

3.3K
Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix10:21

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix

Published on: June 14, 2016

10.1K

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...
21
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...
15
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...
27
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,...
15
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...
22
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...
20