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Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice

Inflammatory reactions activated by pattern recognition receptors (PRRs) on the membrane of innate immune cells play an important role in atherosclerosis. Whether the PRRs of the C-type lectin receptor (CLR) family including Dectin-2 may be involved in the pathogenesis of atherosclerosis remains lar...

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Autores principales: Thiem, Kathrin, Hoeke, Geerte, van den Berg, Susan, Hijmans, Anneke, Jacobs, Cor W. M., Zhou, Enchen, Mol, Isabel M., Mouktaroudi, Maria, Bussink, Johan, Kanneganti, Thirumala D., Lutgens, Esther, Stienstra, Rinke, Tack, Cees J., Netea, Mihai G., Rensen, Patrick C. N., Berbée, Jimmy F. P., van Diepen, Janna A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416398/
https://www.ncbi.nlm.nih.gov/pubmed/30867470
http://dx.doi.org/10.1038/s41598-019-40663-x
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author Thiem, Kathrin
Hoeke, Geerte
van den Berg, Susan
Hijmans, Anneke
Jacobs, Cor W. M.
Zhou, Enchen
Mol, Isabel M.
Mouktaroudi, Maria
Bussink, Johan
Kanneganti, Thirumala D.
Lutgens, Esther
Stienstra, Rinke
Tack, Cees J.
Netea, Mihai G.
Rensen, Patrick C. N.
Berbée, Jimmy F. P.
van Diepen, Janna A.
author_facet Thiem, Kathrin
Hoeke, Geerte
van den Berg, Susan
Hijmans, Anneke
Jacobs, Cor W. M.
Zhou, Enchen
Mol, Isabel M.
Mouktaroudi, Maria
Bussink, Johan
Kanneganti, Thirumala D.
Lutgens, Esther
Stienstra, Rinke
Tack, Cees J.
Netea, Mihai G.
Rensen, Patrick C. N.
Berbée, Jimmy F. P.
van Diepen, Janna A.
author_sort Thiem, Kathrin
collection PubMed
description Inflammatory reactions activated by pattern recognition receptors (PRRs) on the membrane of innate immune cells play an important role in atherosclerosis. Whether the PRRs of the C-type lectin receptor (CLR) family including Dectin-2 may be involved in the pathogenesis of atherosclerosis remains largely unknown. Recently, the CLR-adaptor molecule caspase recruitment domain family member 9 (CARD9) has been suggested to play a role in cardiovascular pathologies as it provides the link between CLR activation and transcription of inflammatory cytokines as well as immune cell recruitment. We therefore evaluated whether hematopoietic deletion of Dectin-2 or CARD9 reduces inflammation and atherosclerosis development. Low-density lipoprotein receptor (Ldlr)-knockout mice were transplanted with bone marrow from wild-type, Dectin-2- or Card9-knockout mice and fed a Western-type diet containing 0.1% (w/w) cholesterol. After 10 weeks, lipid and inflammatory parameters were measured and atherosclerosis development was determined. Deletion of hematopoietic Dectin-2 or CARD9 did not influence plasma triglyceride and cholesterol levels. Deletion of hematopoietic Dectin-2 did not affect atherosclerotic lesion area, immune cell composition, ex vivo cytokine secretion by peritoneal cells or bone marrow derived macrophages. Unexpectedly, deletion of hematopoietic CARD9 increased atherosclerotic lesion formation and lesion severity. Deletion of hematopoietic CARD9 did also not influence circulating immune cell composition and peripheral cytokine secretion. Besides a tendency to a reduced macrophage content within these lesions, plasma MCP-1 levels decreased upon WTD feeding. Deletion of hematopoietic Dectin-2 did not influence atherosclerosis development in hyperlipidemic mice. The absence of CARD9 unexpectedly increased atherosclerotic lesion size and severity, suggesting that the presence of CARD9 may protect against initiation of atherosclerosis development.
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spelling pubmed-64163982019-03-18 Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice Thiem, Kathrin Hoeke, Geerte van den Berg, Susan Hijmans, Anneke Jacobs, Cor W. M. Zhou, Enchen Mol, Isabel M. Mouktaroudi, Maria Bussink, Johan Kanneganti, Thirumala D. Lutgens, Esther Stienstra, Rinke Tack, Cees J. Netea, Mihai G. Rensen, Patrick C. N. Berbée, Jimmy F. P. van Diepen, Janna A. Sci Rep Article Inflammatory reactions activated by pattern recognition receptors (PRRs) on the membrane of innate immune cells play an important role in atherosclerosis. Whether the PRRs of the C-type lectin receptor (CLR) family including Dectin-2 may be involved in the pathogenesis of atherosclerosis remains largely unknown. Recently, the CLR-adaptor molecule caspase recruitment domain family member 9 (CARD9) has been suggested to play a role in cardiovascular pathologies as it provides the link between CLR activation and transcription of inflammatory cytokines as well as immune cell recruitment. We therefore evaluated whether hematopoietic deletion of Dectin-2 or CARD9 reduces inflammation and atherosclerosis development. Low-density lipoprotein receptor (Ldlr)-knockout mice were transplanted with bone marrow from wild-type, Dectin-2- or Card9-knockout mice and fed a Western-type diet containing 0.1% (w/w) cholesterol. After 10 weeks, lipid and inflammatory parameters were measured and atherosclerosis development was determined. Deletion of hematopoietic Dectin-2 or CARD9 did not influence plasma triglyceride and cholesterol levels. Deletion of hematopoietic Dectin-2 did not affect atherosclerotic lesion area, immune cell composition, ex vivo cytokine secretion by peritoneal cells or bone marrow derived macrophages. Unexpectedly, deletion of hematopoietic CARD9 increased atherosclerotic lesion formation and lesion severity. Deletion of hematopoietic CARD9 did also not influence circulating immune cell composition and peripheral cytokine secretion. Besides a tendency to a reduced macrophage content within these lesions, plasma MCP-1 levels decreased upon WTD feeding. Deletion of hematopoietic Dectin-2 did not influence atherosclerosis development in hyperlipidemic mice. The absence of CARD9 unexpectedly increased atherosclerotic lesion size and severity, suggesting that the presence of CARD9 may protect against initiation of atherosclerosis development. Nature Publishing Group UK 2019-03-13 /pmc/articles/PMC6416398/ /pubmed/30867470 http://dx.doi.org/10.1038/s41598-019-40663-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Thiem, Kathrin
Hoeke, Geerte
van den Berg, Susan
Hijmans, Anneke
Jacobs, Cor W. M.
Zhou, Enchen
Mol, Isabel M.
Mouktaroudi, Maria
Bussink, Johan
Kanneganti, Thirumala D.
Lutgens, Esther
Stienstra, Rinke
Tack, Cees J.
Netea, Mihai G.
Rensen, Patrick C. N.
Berbée, Jimmy F. P.
van Diepen, Janna A.
Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice
title Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice
title_full Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice
title_fullStr Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice
title_full_unstemmed Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice
title_short Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice
title_sort deletion of hematopoietic dectin-2 or card9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416398/
https://www.ncbi.nlm.nih.gov/pubmed/30867470
http://dx.doi.org/10.1038/s41598-019-40663-x
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