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Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload.
Sci Rep. 2017 08 23; 7(1):9193.SR

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.

Authors+Show Affiliations

Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS) and National University Health System (NUHS), Singapore, Singapore.Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, Utrecht, The Netherlands. Laboratory of Experimental Cardiology, Department of Cardiology, Heart Lung Center Leiden, Leiden University Medical Center, Leiden, The Netherlands.Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS) and National University Health System (NUHS), Singapore, Singapore.Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS) and National University Health System (NUHS), Singapore, Singapore.Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, Utrecht, The Netherlands.Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS) and National University Health System (NUHS), Singapore, Singapore.Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, Utrecht, The Netherlands.National Heart Centre Singapore, Duke-NUS Graduate Medical School, Singapore, Singapore. Carolyn.Lam@duke-nus.edu.sg. Cardiology, University Medical Center, Groningen, The Netherlands. Carolyn.Lam@duke-nus.edu.sg.Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. D.P.V.deKleijn@umcutrecht.nl. Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS) and National University Health System (NUHS), Singapore, Singapore. D.P.V.deKleijn@umcutrecht.nl. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. D.P.V.deKleijn@umcutrecht.nl. Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. D.P.V.deKleijn@umcutrecht.nl. Netherlands Heart Institute, Utrecht, The Netherlands. D.P.V.deKleijn@umcutrecht.nl.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28835616

Citation

Wang, Jiong-Wei, et al. "Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function and Reduces Fibrosis in Sustained Pressure Overload." Scientific Reports, vol. 7, no. 1, 2017, p. 9193.
Wang JW, Fontes MSC, Wang X, et al. Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload. Sci Rep. 2017;7(1):9193.
Wang, J. W., Fontes, M. S. C., Wang, X., Chong, S. Y., Kessler, E. L., Zhang, Y. N., de Haan, J. J., Arslan, F., de Jager, S. C. A., Timmers, L., van Veen, T. A. B., Lam, C. S. P., & Kleijn, D. P. V. (2017). Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload. Scientific Reports, 7(1), 9193. https://doi.org/10.1038/s41598-017-09451-3
Wang JW, et al. Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function and Reduces Fibrosis in Sustained Pressure Overload. Sci Rep. 2017 08 23;7(1):9193. PubMed PMID: 28835616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload. AU - Wang,Jiong-Wei, AU - Fontes,Magda S C, AU - Wang,Xiaoyuan, AU - Chong,Suet Yen, AU - Kessler,Elise L, AU - Zhang,Ya-Nan, AU - de Haan,Judith J, AU - Arslan,Fatih, AU - de Jager,Saskia C A, AU - Timmers,Leo, AU - van Veen,Toon A B, AU - Lam,Carolyn S P, AU - Kleijn,Dominique P V de, Y1 - 2017/08/23/ PY - 2017/03/20/received PY - 2017/07/25/accepted PY - 2017/8/25/entrez PY - 2017/8/25/pubmed PY - 2019/4/12/medline SP - 9193 EP - 9193 JF - Scientific reports JO - Sci Rep VL - 7 IS - 1 N2 - 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. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/28835616/Leukocytic_Toll_Like_Receptor_2_Deficiency_Preserves_Cardiac_Function_And_Reduces_Fibrosis_In_Sustained_Pressure_Overload_ L2 - https://doi.org/10.1038/s41598-017-09451-3 DB - PRIME DP - Unbound Medicine ER -