title: 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 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.
authors.affiliation: Department of Cardiology, Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Cong-Lin
authors.initials: CL
authors.lastname: Liu
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Marcela M
authors.initials: MM
authors.lastname: Santos
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Cleverson
authors.initials: C
authors.lastname: Fernandes
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Liao
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Karine
authors.initials: K
authors.lastname: Iamarene
authors.affiliation: Department of Cardiology, Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jin-Ying
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Galina K
authors.initials: GK
authors.lastname: Sukhova
authors.affiliation: Department of Cardiology, Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. gshi@rics.bwh.harvard.edu.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA. gshi@rics.bwh.harvard.edu.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002403:Cathepsins / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004549:Elastin / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D051199:Toll-Like Receptor 7 / Q000172:deficiency / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D015850:Interleukin-6; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D003094:Collagen; D004549:Elastin; D002403:Cathepsins; C028217:cathepsin S; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse