Toll-like receptor 7 deficiency protects apolipoprotein E-deficient mice from diet-induced atherosclerosis

Abstract Toll-like receptor 7 (TLR7) mediates autoantigen and viral RNA-induced cytokine production. Increased TLR7 expression in human atherosclerotic lesions suggests its involvement in atherogenesis. Here we demonstrated TLR7 expression in macrophages, smooth muscle cells (SMCs), and endothelial...

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Autores principales:	Cong-Lin Liu, Marcela M. Santos, Cleverson Fernandes, Mengyang Liao, Karine Iamarene, Jin-Ying Zhang, Galina K. Sukhova, Guo-Ping Shi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0745c230f414429ab9e7bee09e14902b
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spelling	oai:doaj.org-article:0745c230f414429ab9e7bee09e14902b2021-12-02T16:07:47ZToll-like receptor 7 deficiency protects apolipoprotein E-deficient mice from diet-induced atherosclerosis10.1038/s41598-017-00977-02045-2322https://doaj.org/article/0745c230f414429ab9e7bee09e14902b2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00977-0https://doaj.org/toc/2045-2322Abstract Toll-like receptor 7 (TLR7) mediates autoantigen and viral RNA-induced cytokine production. Increased TLR7 expression in human atherosclerotic lesions suggests its involvement in atherogenesis. Here we demonstrated TLR7 expression in macrophages, smooth muscle cells (SMCs), and endothelial cells from mouse atherosclerotic lesions. To test a direct participation of TLR7 in atherosclerosis, we crossbred TLR7-deficient (Tlr7 −/−) mice with apolipoprotein E-deficient (Apoe −/−) mice and produced Apoe −/− Tlr7 −/− and Apoe −/− Tlr7 +/+ littermates, followed by feeding them an atherogenic diet to produce atherosclerosis. Compared to Apoe −/− Tlr7 +/+ mice, Apoe −/− Tlr7 −/− mice showed reduced aortic arch and sinus lesion areas. Reduced atherosclerosis in Apoe −/− Tlr7 −/− mice did not affect lesion macrophage-positive area and CD4+ T-cell number per lesion area, but reduced lesion expression of inflammatory markers major histocompatibility complex-class II and IL6, lesion matrix-degrading proteases cathepsin S and matrix metalloproteinase-9, and systemic serum amyloid A levels. TLR7 deficiency also reduced aortic arch SMC loss and lesion intima and media cell apoptosis. However, TLR7 deficiency did not affect aortic wall elastin fragmentation and collagen contents, or plasma lipoproteins. Therefore, TLR7 contributes to atherogenesis in Apoe −/− mice by regulating lesion and systemic inflammation. A TLR7 antagonist may mitigate atherosclerosis.Cong-Lin LiuMarcela M. SantosCleverson FernandesMengyang LiaoKarine IamareneJin-Ying ZhangGalina K. SukhovaGuo-Ping ShiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cong-Lin Liu Marcela M. Santos Cleverson Fernandes Mengyang Liao Karine Iamarene Jin-Ying Zhang Galina K. Sukhova Guo-Ping Shi Toll-like receptor 7 deficiency protects apolipoprotein E-deficient mice from diet-induced atherosclerosis
description	Abstract Toll-like receptor 7 (TLR7) mediates autoantigen and viral RNA-induced cytokine production. Increased TLR7 expression in human atherosclerotic lesions suggests its involvement in atherogenesis. Here we demonstrated TLR7 expression in macrophages, smooth muscle cells (SMCs), and endothelial cells from mouse atherosclerotic lesions. To test a direct participation of TLR7 in atherosclerosis, we crossbred TLR7-deficient (Tlr7 −/−) mice with apolipoprotein E-deficient (Apoe −/−) mice and produced Apoe −/− Tlr7 −/− and Apoe −/− Tlr7 +/+ littermates, followed by feeding them an atherogenic diet to produce atherosclerosis. Compared to Apoe −/− Tlr7 +/+ mice, Apoe −/− Tlr7 −/− mice showed reduced aortic arch and sinus lesion areas. Reduced atherosclerosis in Apoe −/− Tlr7 −/− mice did not affect lesion macrophage-positive area and CD4+ T-cell number per lesion area, but reduced lesion expression of inflammatory markers major histocompatibility complex-class II and IL6, lesion matrix-degrading proteases cathepsin S and matrix metalloproteinase-9, and systemic serum amyloid A levels. TLR7 deficiency also reduced aortic arch SMC loss and lesion intima and media cell apoptosis. However, TLR7 deficiency did not affect aortic wall elastin fragmentation and collagen contents, or plasma lipoproteins. Therefore, TLR7 contributes to atherogenesis in Apoe −/− mice by regulating lesion and systemic inflammation. A TLR7 antagonist may mitigate atherosclerosis.
format	article
author	Cong-Lin Liu Marcela M. Santos Cleverson Fernandes Mengyang Liao Karine Iamarene Jin-Ying Zhang Galina K. Sukhova Guo-Ping Shi
author_facet	Cong-Lin Liu Marcela M. Santos Cleverson Fernandes Mengyang Liao Karine Iamarene Jin-Ying Zhang Galina K. Sukhova Guo-Ping Shi
author_sort	Cong-Lin Liu
title	Toll-like receptor 7 deficiency protects apolipoprotein E-deficient mice from diet-induced atherosclerosis
title_short	Toll-like receptor 7 deficiency protects apolipoprotein E-deficient mice from diet-induced atherosclerosis
title_full	Toll-like receptor 7 deficiency protects apolipoprotein E-deficient mice from diet-induced atherosclerosis
title_fullStr	Toll-like receptor 7 deficiency protects apolipoprotein E-deficient mice from diet-induced atherosclerosis
title_full_unstemmed	Toll-like receptor 7 deficiency protects apolipoprotein E-deficient mice from diet-induced atherosclerosis
title_sort	toll-like receptor 7 deficiency protects apolipoprotein e-deficient mice from diet-induced atherosclerosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0745c230f414429ab9e7bee09e14902b
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Toll-like receptor 7 deficiency protects apolipoprotein E-deficient mice from diet-induced atherosclerosis

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