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Increased expression of blood muscarinic receptors in patients with reflex syncope
AIMS: Pathophysiology of reflex syncope is not fully understood but a vagal overactivity might be involved in this syncope. Previously, overexpression of muscarinic M(2) receptors and acetylcholinesterase was found in particular in the heart and in lymphocytes of rabbits with vagal overactivity as w...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638918/ https://www.ncbi.nlm.nih.gov/pubmed/31318899 http://dx.doi.org/10.1371/journal.pone.0219598 |
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author | Beutelstetter, Maxime Livolsi, Angelo Greney, Hugues Helms, Pauline Schmidt-Mutter, Catherine De Melo, Charlie Roul, Gerald Zores, Florian Bolle, Alexandre Dali-Youcef, Nassim Beaugey, Magali Simon, Alban Niederhoffer, Nathalie Regnard, Jacques Bouhaddi, Malika Adamopoulos, Chris Schaeffer, Mickael Sauleau, Erik Bousquet, Pascal |
author_facet | Beutelstetter, Maxime Livolsi, Angelo Greney, Hugues Helms, Pauline Schmidt-Mutter, Catherine De Melo, Charlie Roul, Gerald Zores, Florian Bolle, Alexandre Dali-Youcef, Nassim Beaugey, Magali Simon, Alban Niederhoffer, Nathalie Regnard, Jacques Bouhaddi, Malika Adamopoulos, Chris Schaeffer, Mickael Sauleau, Erik Bousquet, Pascal |
author_sort | Beutelstetter, Maxime |
collection | PubMed |
description | AIMS: Pathophysiology of reflex syncope is not fully understood but a vagal overactivity might be involved in this syncope. Previously, overexpression of muscarinic M(2) receptors and acetylcholinesterase was found in particular in the heart and in lymphocytes of rabbits with vagal overactivity as well as in hearts of Sudden Infant Death Syndromes. The aim of this present study was to look at M(2) receptor expression in blood of patients with reflex syncope. The second objective was to measure acetylcholinesterase expression in these patients. METHODS AND RESULTS: 136 subjects were enrolled. This monocenter study pooled 45 adults exhibiting recurrent reflex syncope compared with 32 healthy adult volunteers (18–50 years) and 38 children exhibiting reflex syncope requiring hospitalization compared with 21 controls (1–17 years). One blood sample was taken from each subject and blood mRNA expression of M2 receptors was assessed by qRT-PCR. Taking into account the non-symmetric distributions of values in both groups, statistical interferences were assessed using bayesian techniques. A M(2) receptor overexpression was observed in adult and pediatric patients compared to controls. The medians [q1;q3] were 0.9 [0.3;1.9] in patients versus 0.2 [0.1;1.0] in controls; the probability that M(2) receptor expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.99. Acetylcholinesterase expression was also increased 0.7 [0.4;1.6] in patients versus 0.4 [0.2;1.1] in controls; the probability that acetylcholinesterase expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.97. Both in adults and children, the expression ratio of M(2) receptors over acetylcholinesterase was greater in the patient group compared with the control group. CONCLUSION: M(2) receptor overexpression has been detected in the blood of both, adults and children, exhibiting reflex syncope. As in our experimental model, i.e. rabbits with vagal overactivity, acetylcholinesterase overexpression was associated with M(2) receptor overexpression. For the first time, biological abnormalities are identified in vagal syncope in which only clinical signs are, so far, taken into account for differential diagnosis and therapeutic management. Further work will be needed to validate potential biomarkers of risk or severity associated with the cholinergic system. |
format | Online Article Text |
id | pubmed-6638918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-66389182019-07-25 Increased expression of blood muscarinic receptors in patients with reflex syncope Beutelstetter, Maxime Livolsi, Angelo Greney, Hugues Helms, Pauline Schmidt-Mutter, Catherine De Melo, Charlie Roul, Gerald Zores, Florian Bolle, Alexandre Dali-Youcef, Nassim Beaugey, Magali Simon, Alban Niederhoffer, Nathalie Regnard, Jacques Bouhaddi, Malika Adamopoulos, Chris Schaeffer, Mickael Sauleau, Erik Bousquet, Pascal PLoS One Research Article AIMS: Pathophysiology of reflex syncope is not fully understood but a vagal overactivity might be involved in this syncope. Previously, overexpression of muscarinic M(2) receptors and acetylcholinesterase was found in particular in the heart and in lymphocytes of rabbits with vagal overactivity as well as in hearts of Sudden Infant Death Syndromes. The aim of this present study was to look at M(2) receptor expression in blood of patients with reflex syncope. The second objective was to measure acetylcholinesterase expression in these patients. METHODS AND RESULTS: 136 subjects were enrolled. This monocenter study pooled 45 adults exhibiting recurrent reflex syncope compared with 32 healthy adult volunteers (18–50 years) and 38 children exhibiting reflex syncope requiring hospitalization compared with 21 controls (1–17 years). One blood sample was taken from each subject and blood mRNA expression of M2 receptors was assessed by qRT-PCR. Taking into account the non-symmetric distributions of values in both groups, statistical interferences were assessed using bayesian techniques. A M(2) receptor overexpression was observed in adult and pediatric patients compared to controls. The medians [q1;q3] were 0.9 [0.3;1.9] in patients versus 0.2 [0.1;1.0] in controls; the probability that M(2) receptor expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.99. Acetylcholinesterase expression was also increased 0.7 [0.4;1.6] in patients versus 0.4 [0.2;1.1] in controls; the probability that acetylcholinesterase expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.97. Both in adults and children, the expression ratio of M(2) receptors over acetylcholinesterase was greater in the patient group compared with the control group. CONCLUSION: M(2) receptor overexpression has been detected in the blood of both, adults and children, exhibiting reflex syncope. As in our experimental model, i.e. rabbits with vagal overactivity, acetylcholinesterase overexpression was associated with M(2) receptor overexpression. For the first time, biological abnormalities are identified in vagal syncope in which only clinical signs are, so far, taken into account for differential diagnosis and therapeutic management. Further work will be needed to validate potential biomarkers of risk or severity associated with the cholinergic system. Public Library of Science 2019-07-18 /pmc/articles/PMC6638918/ /pubmed/31318899 http://dx.doi.org/10.1371/journal.pone.0219598 Text en © 2019 Beutelstetter et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Beutelstetter, Maxime Livolsi, Angelo Greney, Hugues Helms, Pauline Schmidt-Mutter, Catherine De Melo, Charlie Roul, Gerald Zores, Florian Bolle, Alexandre Dali-Youcef, Nassim Beaugey, Magali Simon, Alban Niederhoffer, Nathalie Regnard, Jacques Bouhaddi, Malika Adamopoulos, Chris Schaeffer, Mickael Sauleau, Erik Bousquet, Pascal Increased expression of blood muscarinic receptors in patients with reflex syncope |
title | Increased expression of blood muscarinic receptors in patients with reflex syncope |
title_full | Increased expression of blood muscarinic receptors in patients with reflex syncope |
title_fullStr | Increased expression of blood muscarinic receptors in patients with reflex syncope |
title_full_unstemmed | Increased expression of blood muscarinic receptors in patients with reflex syncope |
title_short | Increased expression of blood muscarinic receptors in patients with reflex syncope |
title_sort | increased expression of blood muscarinic receptors in patients with reflex syncope |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638918/ https://www.ncbi.nlm.nih.gov/pubmed/31318899 http://dx.doi.org/10.1371/journal.pone.0219598 |
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