Markedly reduced myocardial expression of γ-protocadherins and long non-coding RNAs in patients with heart disease.

Cadherin Related Proteins Cadherins Heart Diseases / genetics Humans Prospective Studies RNA, Long Noncoding / genetics
Aortic valve replacement Cardiovascular disease Coronary artery bypass graft Inflammation Non-coding RNAs Protocadherins

Journal

International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291

Informations de publication

Date de publication:
01 Dec 2021
Historique:
received: 14 04 2021
revised: 16 09 2021
accepted: 22 09 2021
pubmed: 1 10 2021
medline: 9 11 2021
entrez: 30 9 2021
Statut: ppublish

Résumé

Adverse cardiac remodeling and tissue damage following heart disease is strongly associated with chronic low grade inflammation. The mechanisms underlying persisting inflammatory signals are not fully understood, but may involve defective and/or non-responsive transcriptional and post-transcriptional regulatory mechanisms. In the current study, we aimed to identify novel mediators and pathways involved in processes associated with inflammation in the development and maintenance of cardiac disease. We performed RNA sequencing analysis of cardiac tissue from patients undergoing coronary artery bypass grafting (CABG) or aortic valve replacement (AVR) and compared with control tissue from multi-organ donors. Our results confirmed previous findings of a marked upregulated inflammatory state, but more importantly, we found pronounced reduction of non-protein coding genes, particularly long non-coding RNAs (lncRNA), including several lncRNAs known to be associated with inflammation and/or cardiovascular disease. In addition, Gene Set Enrichment Analysis revealed markedly downregulated microRNA pathways, resulting in aberrant expression of other genes, particularly γ-protocadherins. Our data suggest that aberrant expression of non-coding gene regulators comprise crucial keys in the progression of heart disease, and may be pivotal for chronic low grade inflammation associated with cardiac dysfunction. By unmasking atypical γ-protocadherin expression as a prospective genetic biomarker of myocardial dysfunction, our study provides new insight into the complex molecular framework of heart disease. Creating new approaches to modify non-coding gene regulators, such as those identified in the current study, may define novel strategies to shift γ-protocadherin expression, thereby normalizing part of the molecular architecture associated with heart disease.

Sections du résumé

BACKGROUND BACKGROUND
Adverse cardiac remodeling and tissue damage following heart disease is strongly associated with chronic low grade inflammation. The mechanisms underlying persisting inflammatory signals are not fully understood, but may involve defective and/or non-responsive transcriptional and post-transcriptional regulatory mechanisms. In the current study, we aimed to identify novel mediators and pathways involved in processes associated with inflammation in the development and maintenance of cardiac disease.
METHODS AND RESULTS RESULTS
We performed RNA sequencing analysis of cardiac tissue from patients undergoing coronary artery bypass grafting (CABG) or aortic valve replacement (AVR) and compared with control tissue from multi-organ donors. Our results confirmed previous findings of a marked upregulated inflammatory state, but more importantly, we found pronounced reduction of non-protein coding genes, particularly long non-coding RNAs (lncRNA), including several lncRNAs known to be associated with inflammation and/or cardiovascular disease. In addition, Gene Set Enrichment Analysis revealed markedly downregulated microRNA pathways, resulting in aberrant expression of other genes, particularly γ-protocadherins.
CONCLUSIONS CONCLUSIONS
Our data suggest that aberrant expression of non-coding gene regulators comprise crucial keys in the progression of heart disease, and may be pivotal for chronic low grade inflammation associated with cardiac dysfunction. By unmasking atypical γ-protocadherin expression as a prospective genetic biomarker of myocardial dysfunction, our study provides new insight into the complex molecular framework of heart disease. Creating new approaches to modify non-coding gene regulators, such as those identified in the current study, may define novel strategies to shift γ-protocadherin expression, thereby normalizing part of the molecular architecture associated with heart disease.

Identifiants

DOI: 10.1016/j.ijcard.2021.09.046 PMID: 34592247
pubmed: 34592247
pii: S0167-5273(21)01490-X
doi: 10.1016/j.ijcard.2021.09.046
pii:
doi:

Substances chimiques

Cadherin Related Proteins 0
Cadherins 0
Gamma-protocadherins 0
RNA, Long Noncoding 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

149-159

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

Joakim Sandstedt (J)

Department of Clinical Chemistry, Sahlgrenska University Hospital and Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.

Kristina Vukusic (K)

Department of Clinical Chemistry, Sahlgrenska University Hospital and Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.

Elham Rekabdar (E)

Genomics Core Facility, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden.

Göran Dellgren (G)

Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.

Anders Jeppsson (A)

Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.

Lillemor Mattsson Hultén (L)

Department of Clinical Chemistry, Sahlgrenska University Hospital and Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.

Victoria Rotter Sopasakis (V)

Department of Clinical Chemistry, Sahlgrenska University Hospital and Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden. Electronic address: victoria.rotter@clinchem.gu.se.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines apparentées aux cadhérines › Markedly reduced myocardial expression of...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes de surface › Molécules d'adhérence cellulaire › Cadhérines › Markedly reduced myocardial expression of...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Markedly reduced myocardial expression of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Markedly reduced myocardial expression of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Markedly reduced myocardial expression of...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › ARN long non codant › Markedly reduced myocardial expression of...