Release of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery

Anne Vejlstrup,1 Ann Merete Møller,2 Claus Henrik Nielsen,1,3,* Dres Damgaard1,3,*1Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Department of Anaesthesiology, Herlev Hospital, Herlev,...

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Autores principales:	Vejlstrup A, Møller AM, Nielsen CH, Damgaard D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Citrullination peptidylarginine deiminase (PAD) inflammation coronary artery bypass grafting (CABG) cardiopulmonary bypass (CPB) Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/89cdafd1c4e54926880e0cffa71f5b19
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spelling	oai:doaj.org-article:89cdafd1c4e54926880e0cffa71f5b192021-12-02T03:57:37ZRelease of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery1178-7031https://doaj.org/article/89cdafd1c4e54926880e0cffa71f5b192019-05-01T00:00:00Zhttps://www.dovepress.com/release-of-active-peptidylarginine-deiminase-into-the-circulation-duri-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Anne Vejlstrup,1 Ann Merete Møller,2 Claus Henrik Nielsen,1,3,* Dres Damgaard1,3,1Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Department of Anaesthesiology, Herlev Hospital, Herlev, Denmark; 3Section for Periodontology, Microbiology and Community Dentistry, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkThese authors contributed equally to this workPurpose: Peptidylarginine deiminase (PAD) catalyzes citrullination, a post-translational modification that can alter structure, function and antigenicity of proteins. Citrullination in the lungs due to smoking is believed to initiate an anti-citrulline immune response in rheumatoid arthritis. Citrullination in other inflamed organs has also been demonstrated, but it is not known whether smoking or inflammatory processes in general result in release of relevant amounts of PAD into the circulation with potential to cause citrullination of proteins at various anatomical sites. Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) induces an acute systemic inflammation response. In the present study, we investigate whether smoking or acute systemic inflammation causes release of PAD into the circulation.Patients and methods: This study included 36 patients with coronary heart disease (16 smokers and 20 non-smokers) undergoing CABG surgery with CPB. Circulating levels of PAD2 and PAD4, PAD activity, the neutrophil activation markers MPO, MMP-9 and lipocalin-2, the cytokines IL-6 and IL-10, and the chemokine CXCL8 were measured 2 hrs preoperatively and 2 hrs postoperatively.Results: At baseline, serum PAD2 and PAD4 concentration did not differ between smokers and non-smokers. However, serum from non-smokers contained higher PAD activity than serum from smokers. Circulating PAD2 levels and PAD activity increased markedly in both groups after surgery, as did all neutrophil activation markers, cytokines and chemokine. PAD2 levels correlated with neutrophil activation markers, but not with cytokine and chemokine levels.Conclusion: Blood levels of PAD2 did not differ significantly between smokers and non-smokers, but smokers had decreased PAD activity in the circulation. PAD2 levels and PAD activity increased in blood during inflammation induced by CABG with CPB. This suggests that acute inflammation, ischemia or reperfusion, or a combination of these, leads to systemic spreading of enzymatically active PAD, which may affect protein function and induce generation of citrullinated self-antigens.Keywords: citrullination, peptidylarginine deiminase, PAD, inflammation, coronary artery bypass grafting, CABG, cardiopulmonary bypass, CPBVejlstrup AMøller AMNielsen CHDamgaard DDove Medical PressarticleCitrullinationpeptidylarginine deiminase (PAD)inflammationcoronary artery bypass grafting (CABG)cardiopulmonary bypass (CPB)PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 12, Pp 137-144 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Citrullination peptidylarginine deiminase (PAD) inflammation coronary artery bypass grafting (CABG) cardiopulmonary bypass (CPB) Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Citrullination peptidylarginine deiminase (PAD) inflammation coronary artery bypass grafting (CABG) cardiopulmonary bypass (CPB) Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Vejlstrup A Møller AM Nielsen CH Damgaard D Release of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery
description	Anne Vejlstrup,1 Ann Merete Møller,2 Claus Henrik Nielsen,1,3,* Dres Damgaard1,3,1Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Department of Anaesthesiology, Herlev Hospital, Herlev, Denmark; 3Section for Periodontology, Microbiology and Community Dentistry, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkThese authors contributed equally to this workPurpose: Peptidylarginine deiminase (PAD) catalyzes citrullination, a post-translational modification that can alter structure, function and antigenicity of proteins. Citrullination in the lungs due to smoking is believed to initiate an anti-citrulline immune response in rheumatoid arthritis. Citrullination in other inflamed organs has also been demonstrated, but it is not known whether smoking or inflammatory processes in general result in release of relevant amounts of PAD into the circulation with potential to cause citrullination of proteins at various anatomical sites. Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) induces an acute systemic inflammation response. In the present study, we investigate whether smoking or acute systemic inflammation causes release of PAD into the circulation.Patients and methods: This study included 36 patients with coronary heart disease (16 smokers and 20 non-smokers) undergoing CABG surgery with CPB. Circulating levels of PAD2 and PAD4, PAD activity, the neutrophil activation markers MPO, MMP-9 and lipocalin-2, the cytokines IL-6 and IL-10, and the chemokine CXCL8 were measured 2 hrs preoperatively and 2 hrs postoperatively.Results: At baseline, serum PAD2 and PAD4 concentration did not differ between smokers and non-smokers. However, serum from non-smokers contained higher PAD activity than serum from smokers. Circulating PAD2 levels and PAD activity increased markedly in both groups after surgery, as did all neutrophil activation markers, cytokines and chemokine. PAD2 levels correlated with neutrophil activation markers, but not with cytokine and chemokine levels.Conclusion: Blood levels of PAD2 did not differ significantly between smokers and non-smokers, but smokers had decreased PAD activity in the circulation. PAD2 levels and PAD activity increased in blood during inflammation induced by CABG with CPB. This suggests that acute inflammation, ischemia or reperfusion, or a combination of these, leads to systemic spreading of enzymatically active PAD, which may affect protein function and induce generation of citrullinated self-antigens.Keywords: citrullination, peptidylarginine deiminase, PAD, inflammation, coronary artery bypass grafting, CABG, cardiopulmonary bypass, CPB
format	article
author	Vejlstrup A Møller AM Nielsen CH Damgaard D
author_facet	Vejlstrup A Møller AM Nielsen CH Damgaard D
author_sort	Vejlstrup A
title	Release of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery
title_short	Release of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery
title_full	Release of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery
title_fullStr	Release of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery
title_full_unstemmed	Release of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery
title_sort	release of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/89cdafd1c4e54926880e0cffa71f5b19
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Release of active peptidylarginine deiminase into the circulation during acute inflammation induced by coronary artery bypass surgery

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