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...

Descripción completa

Guardado en:
Detalles Bibliográficos
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:
R
Q
Acceso en línea:https://doaj.org/article/0745c230f414429ab9e7bee09e14902b
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario: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.