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Updated: Aug 21, 2026

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

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Beyond sarcomere genetics: proteomic insights into hypertrophic cardiomyopathy

Zachery R Gregorich1, Zhan Gao2, Kalina J Rossler2

  • 1Department of Animal & Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706 USA.

Biophysical Reviews
|August 20, 2026
PubMed

Insights

Hypertrophic cardiomyopathy (HCM) is not solely genetic; proteomics reveals broad molecular changes across heart cells. This research highlights proteomics for understanding HCM mechanisms and finding new treatments.

Area of Science:

  • Cardiovascular Biology
  • Proteomics
  • Molecular Medicine

Background:

  • Hypertrophic cardiomyopathy (HCM) is traditionally viewed as a monogenic disorder linked to sarcomere gene variants.
  • However, only a third of HCM cases are genotype-positive, indicating other contributing factors.
  • Incomplete penetrance and phenotypic heterogeneity challenge the purely genetic model of HCM.

Purpose of the Study:

  • To explore the molecular underpinnings of HCM beyond genetics.
  • To leverage recent advances in proteomics to analyze HCM myocardium.
  • To redefine the understanding of HCM pathobiology through proteomic insights.

Main Methods:

  • Review of top-down and bottom-up proteomics studies on human HCM myocardium.
  • Analysis of proteomic data to identify molecular remodeling across cellular compartments.
  • Integration of genetic and proteomic findings to model HCM pathobiology.

Main Results:

  • HCM exhibits widespread proteomic alterations beyond the sarcomere.
  • Molecular remodeling affects multiple cellular compartments, including the sarcoplasmic reticulum, cytoskeleton, mitochondria, and nucleus.
  • Diverse genetic causes of HCM converge on shared downstream proteomic phenotypes.

Conclusions:

  • HCM pathobiology involves extensive molecular remodeling across various cellular components.
  • Proteomics offers a powerful lens to understand HCM mechanisms, disease modifiers, and therapeutic targets.
  • A unified model suggests diverse HCM genotypes lead to common proteomic changes.

Keywords:
Hypertrophic cardiomyopathyProteomic insightsSarcomere genetics

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