Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload

Abstract An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis and dysfunction in sustained pressur...

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Autores principales:	Jiong-Wei Wang, Magda S. C. Fontes, Xiaoyuan Wang, Suet Yen Chong, Elise L. Kessler, Ya-Nan Zhang, Judith J. de Haan, Fatih Arslan, Saskia C. A. de Jager, Leo Timmers, Toon A. B. van Veen, Carolyn S. P. Lam, Dominique P. V. de Kleijn
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d91281989b32469aa064567a69b66e0f
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spelling	oai:doaj.org-article:d91281989b32469aa064567a69b66e0f2021-12-02T16:06:27ZLeukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload10.1038/s41598-017-09451-32045-2322https://doaj.org/article/d91281989b32469aa064567a69b66e0f2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09451-3https://doaj.org/toc/2045-2322Abstract An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis and dysfunction in sustained pressure overload. We induced pressure overload via transverse aortic constriction (TAC) in TLR2−/− and wild type (WT) mice, and followed temporal changes over 8 weeks. Despite similar increases in heart weight, left ventricular (LV) ejection fraction (EF) and diastolic function (mitral E/A ratio) were preserved in TLR2−/− mice but impaired in WT mice following TAC. TAC produced less LV fibrosis in TLR2−/− mice associated with lower mRNA levels of collagen genes (Col1a1 and Col3a1) and lower protein level of TGFbeta1, compared to WT mice. Following TAC, the influx of macrophages and CD3 T cells into LV was similar between TLR2−/− and WT mice, whereas levels of cyto/chemokines were lower in the heart and plasma in TLR2−/− mice. TLR2−/− bone marrow-derived cells protected against LVEF decline and fibrosis following TAC. Our findings show that leukocytic TLR2 deficiency protects against LV dysfunction and fibrosis probably via a reduction in inflammatory signaling in sustained pressure overload.Jiong-Wei WangMagda S. C. FontesXiaoyuan WangSuet Yen ChongElise L. KesslerYa-Nan ZhangJudith J. de HaanFatih ArslanSaskia C. A. de JagerLeo TimmersToon A. B. van VeenCarolyn S. P. LamDominique P. V. de KleijnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiong-Wei Wang Magda S. C. Fontes Xiaoyuan Wang Suet Yen Chong Elise L. Kessler Ya-Nan Zhang Judith J. de Haan Fatih Arslan Saskia C. A. de Jager Leo Timmers Toon A. B. van Veen Carolyn S. P. Lam Dominique P. V. de Kleijn Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload
description	Abstract An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis and dysfunction in sustained pressure overload. We induced pressure overload via transverse aortic constriction (TAC) in TLR2−/− and wild type (WT) mice, and followed temporal changes over 8 weeks. Despite similar increases in heart weight, left ventricular (LV) ejection fraction (EF) and diastolic function (mitral E/A ratio) were preserved in TLR2−/− mice but impaired in WT mice following TAC. TAC produced less LV fibrosis in TLR2−/− mice associated with lower mRNA levels of collagen genes (Col1a1 and Col3a1) and lower protein level of TGFbeta1, compared to WT mice. Following TAC, the influx of macrophages and CD3 T cells into LV was similar between TLR2−/− and WT mice, whereas levels of cyto/chemokines were lower in the heart and plasma in TLR2−/− mice. TLR2−/− bone marrow-derived cells protected against LVEF decline and fibrosis following TAC. Our findings show that leukocytic TLR2 deficiency protects against LV dysfunction and fibrosis probably via a reduction in inflammatory signaling in sustained pressure overload.
format	article
author	Jiong-Wei Wang Magda S. C. Fontes Xiaoyuan Wang Suet Yen Chong Elise L. Kessler Ya-Nan Zhang Judith J. de Haan Fatih Arslan Saskia C. A. de Jager Leo Timmers Toon A. B. van Veen Carolyn S. P. Lam Dominique P. V. de Kleijn
author_facet	Jiong-Wei Wang Magda S. C. Fontes Xiaoyuan Wang Suet Yen Chong Elise L. Kessler Ya-Nan Zhang Judith J. de Haan Fatih Arslan Saskia C. A. de Jager Leo Timmers Toon A. B. van Veen Carolyn S. P. Lam Dominique P. V. de Kleijn
author_sort	Jiong-Wei Wang
title	Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload
title_short	Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload
title_full	Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload
title_fullStr	Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload
title_full_unstemmed	Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload
title_sort	leukocytic toll-like receptor 2 deficiency preserves cardiac function and reduces fibrosis in sustained pressure overload
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d91281989b32469aa064567a69b66e0f
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Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload

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