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Cigarette Smoking‐Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets

BACKGROUND: Cigarette smoking plays a major role in cardiovascular diseases. The acute effects of cigarette smoking produce central nervous system–mediated activation of the sympathetic nervous system. The overactive sympathetic nervous system stimulates the secretion of serotonin (5‐HT) and catecho...

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Autores principales: Lowery, Curtis Lee, Elliott, Clay, Cooper, Anthonya, Hadden, Coedy, Sonon, Roberto N., Azadi, Parastoo, Williams, D. Keith, Marsh, James D., Woulfe, Donna S., Kilic, Fusun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524091/
https://www.ncbi.nlm.nih.gov/pubmed/28522678
http://dx.doi.org/10.1161/JAHA.116.005465
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author Lowery, Curtis Lee
Elliott, Clay
Cooper, Anthonya
Hadden, Coedy
Sonon, Roberto N.
Azadi, Parastoo
Williams, D. Keith
Marsh, James D.
Woulfe, Donna S.
Kilic, Fusun
author_facet Lowery, Curtis Lee
Elliott, Clay
Cooper, Anthonya
Hadden, Coedy
Sonon, Roberto N.
Azadi, Parastoo
Williams, D. Keith
Marsh, James D.
Woulfe, Donna S.
Kilic, Fusun
author_sort Lowery, Curtis Lee
collection PubMed
description BACKGROUND: Cigarette smoking plays a major role in cardiovascular diseases. The acute effects of cigarette smoking produce central nervous system–mediated activation of the sympathetic nervous system. The overactive sympathetic nervous system stimulates the secretion of serotonin (5‐HT) and catecholamine into blood at supraphysiological levels. The correlation between these pathological conditions induced by smoking and the increased risk of thrombosis has not been thoroughly investigated. The goal of our study was to explore cigarette smoking–associated changes in platelet biology mediated by elevated 5‐HT and catecholamine levels in blood plasma. METHODS AND RESULTS: Using blood samples collected from healthy nonsmokers and smokers (15 minutes after smoking), we determined that cigarette smoking increased the plasma 5‐HT/catecholamine concentration by several fold and the percent aggregation of platelets 2‐fold. Liquid chromatography–tandem mass spectrometry analysis of proteins eluted from platelet plasma membranes of smokers and nonsmokers demonstrated that GTPase‐activating proteins and proteins participating in the actin cytoskeletal network were differentially and significantly elevated in smokers' platelet membranes compared with those of nonsmokers. Interestingly, Matrix‐assisted laser desorption/ionization–mass spectrometry analyses of the glycans eluted from platelet plasma membranes of the smokers demonstrated that the level and structures of glycans are different from the nonsmokers' platelet surface glycans. Pharmacological blockade of 5‐HT or catecholamine receptors counteracted the 5‐HT/catecholamine‐mediated aggregation and altered the level and composition of glycan on platelet surfaces. CONCLUSIONS: Based on our findings, we propose that smoking‐associated 5‐HT/catecholamine signaling accelerates the trafficking dynamics of platelets, and this remodels the surface proteins and glycans and predisposes platelets to hyperactive levels. Smokers' platelets also had correspondingly higher resting concentrations of intracellular calcium and transglutaminase activity. These findings suggest a link among smoking, platelet 5‐HT, catecholamine signaling, and their downstream effectors—including phospholipase C and inositol‐1,4,5‐triphosphate pathways—resulting in an increased tonic level of platelet activation in smokers.
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spelling pubmed-55240912017-08-02 Cigarette Smoking‐Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets Lowery, Curtis Lee Elliott, Clay Cooper, Anthonya Hadden, Coedy Sonon, Roberto N. Azadi, Parastoo Williams, D. Keith Marsh, James D. Woulfe, Donna S. Kilic, Fusun J Am Heart Assoc Original Research BACKGROUND: Cigarette smoking plays a major role in cardiovascular diseases. The acute effects of cigarette smoking produce central nervous system–mediated activation of the sympathetic nervous system. The overactive sympathetic nervous system stimulates the secretion of serotonin (5‐HT) and catecholamine into blood at supraphysiological levels. The correlation between these pathological conditions induced by smoking and the increased risk of thrombosis has not been thoroughly investigated. The goal of our study was to explore cigarette smoking–associated changes in platelet biology mediated by elevated 5‐HT and catecholamine levels in blood plasma. METHODS AND RESULTS: Using blood samples collected from healthy nonsmokers and smokers (15 minutes after smoking), we determined that cigarette smoking increased the plasma 5‐HT/catecholamine concentration by several fold and the percent aggregation of platelets 2‐fold. Liquid chromatography–tandem mass spectrometry analysis of proteins eluted from platelet plasma membranes of smokers and nonsmokers demonstrated that GTPase‐activating proteins and proteins participating in the actin cytoskeletal network were differentially and significantly elevated in smokers' platelet membranes compared with those of nonsmokers. Interestingly, Matrix‐assisted laser desorption/ionization–mass spectrometry analyses of the glycans eluted from platelet plasma membranes of the smokers demonstrated that the level and structures of glycans are different from the nonsmokers' platelet surface glycans. Pharmacological blockade of 5‐HT or catecholamine receptors counteracted the 5‐HT/catecholamine‐mediated aggregation and altered the level and composition of glycan on platelet surfaces. CONCLUSIONS: Based on our findings, we propose that smoking‐associated 5‐HT/catecholamine signaling accelerates the trafficking dynamics of platelets, and this remodels the surface proteins and glycans and predisposes platelets to hyperactive levels. Smokers' platelets also had correspondingly higher resting concentrations of intracellular calcium and transglutaminase activity. These findings suggest a link among smoking, platelet 5‐HT, catecholamine signaling, and their downstream effectors—including phospholipase C and inositol‐1,4,5‐triphosphate pathways—resulting in an increased tonic level of platelet activation in smokers. John Wiley and Sons Inc. 2017-05-18 /pmc/articles/PMC5524091/ /pubmed/28522678 http://dx.doi.org/10.1161/JAHA.116.005465 Text en © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Lowery, Curtis Lee
Elliott, Clay
Cooper, Anthonya
Hadden, Coedy
Sonon, Roberto N.
Azadi, Parastoo
Williams, D. Keith
Marsh, James D.
Woulfe, Donna S.
Kilic, Fusun
Cigarette Smoking‐Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets
title Cigarette Smoking‐Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets
title_full Cigarette Smoking‐Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets
title_fullStr Cigarette Smoking‐Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets
title_full_unstemmed Cigarette Smoking‐Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets
title_short Cigarette Smoking‐Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets
title_sort cigarette smoking‐associated alterations in serotonin/adrenalin signaling pathways of platelets
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524091/
https://www.ncbi.nlm.nih.gov/pubmed/28522678
http://dx.doi.org/10.1161/JAHA.116.005465
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