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Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic

Christina J Codden1, Michael T Chin1,2

  • 1Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.

International Journal of Molecular Sciences
|January 21, 2022
PubMed

Insights

Hypertrophic Cardiomyopathy (HCM) involves genetic changes affecting heart muscle. This study compares obstructive and nonobstructive HCM, revealing distinct cell communication patterns crucial for understanding disease progression and personalized treatment.

Area of Science:

  • Cardiology
  • Genetics
  • Bioinformatics

Background:

  • Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disorder.
  • HCM presents with unexplained left ventricular hypertrophy, with or without left ventricular outflow tract (LVOT) obstruction.
  • Previous studies used single-nuclei RNA sequencing (snRNA-seq) in HCM, but direct comparisons between obstructive and nonobstructive phenotypes are lacking.

Purpose of the Study:

  • To perform a bioinformatic analysis comparing snRNA-seq data from obstructive and nonobstructive HCM patient samples.
  • To identify differentially expressed genes and distinct intercellular communication patterns in the two HCM phenotypes.

Main Methods:

  • Bioinformatic analysis of existing HCM snRNA-seq datasets.
  • Differential gene expression analysis.
  • Intercellular communication pathway analysis.

Main Results:

  • Identified 37 differentially expressed genes in cardiomyocytes and other cell types, linked to aging, muscle contraction, cell motility, and extracellular matrix.
  • Observed generally reduced intercellular communication in HCM, with specific alterations in pathways like growth factor binding and integrin binding.
  • Found increased communication in nonobstructive HCM involving adenylate cyclase binding, calcium channel activity, and serine-threonine kinase activity.
  • Noted increased communication between neurons/fibroblasts and immune cells, and enhanced endothelial cell communication, mediated by integrin-β1.

Conclusions:

  • Common and distinct molecular mechanisms contribute to the pathogenesis of obstructive and nonobstructive HCM.
  • Findings highlight specific cellular communication pathways that differ between HCM subtypes.
  • These insights offer potential for personalized management strategies tailored to different HCM phenotypes.

Keywords:
Hypertrophic Cardiomyopathydendritic cellsintegrin-β1left ventricular outflow tract obstructionsingle-nucleus RNA-sequencing

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