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

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy with or without left ventricular outflow tract (LVOT) obstruction. Single-nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples has reveal...

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Autores principales: Codden, Christina J., Chin, Michael T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780670/
https://www.ncbi.nlm.nih.gov/pubmed/35055131
http://dx.doi.org/10.3390/ijms23020946
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author Codden, Christina J.
Chin, Michael T.
author_facet Codden, Christina J.
Chin, Michael T.
author_sort Codden, Christina J.
collection PubMed
description Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy with or without left ventricular outflow tract (LVOT) obstruction. Single-nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples has revealed alterations in communication between various cell types, but no direct and integrated comparison between the two HCM phenotypes has been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility, and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding, and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication, and in endothelial cell communication to other cell types, largely through changes in the expression of integrin-β1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for the personalized management of different HCM phenotypes.
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spelling pubmed-87806702022-01-22 Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy Codden, Christina J. Chin, Michael T. Int J Mol Sci Article Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy with or without left ventricular outflow tract (LVOT) obstruction. Single-nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples has revealed alterations in communication between various cell types, but no direct and integrated comparison between the two HCM phenotypes has been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility, and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding, and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication, and in endothelial cell communication to other cell types, largely through changes in the expression of integrin-β1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for the personalized management of different HCM phenotypes. MDPI 2022-01-15 /pmc/articles/PMC8780670/ /pubmed/35055131 http://dx.doi.org/10.3390/ijms23020946 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Codden, Christina J.
Chin, Michael T.
Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy
title Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy
title_full Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy
title_fullStr Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy
title_full_unstemmed Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy
title_short Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy
title_sort common and distinctive intercellular communication patterns in human obstructive and nonobstructive hypertrophic cardiomyopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780670/
https://www.ncbi.nlm.nih.gov/pubmed/35055131
http://dx.doi.org/10.3390/ijms23020946
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