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: Cong-Lin Liu, Marcela M Santos, Cleverson Fernandes, Mengyang Liao, Karine Iamarene, Jin-Ying Zhang, Galina K Sukhova, Guo-Ping Shi
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 847 (04 12 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28405010 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Interleukin-6
• Membrane Glycoproteins
• Tlr7 protein, mouse
• Toll-Like Receptor 7
• Collagen
• Elastin
• Cathepsins
• cathepsin S
• Matrix Metalloproteinase 9
• Mmp9 protein, mouse

Topics

• Animals
• Aorta (metabolism, pathology)
• Apolipoproteins E (deficiency, genetics)
• Atherosclerosis (etiology, genetics, metabolism)
• CD4-Positive T-Lymphocytes (metabolism)
• Cathepsins (metabolism)
• Cells, Cultured
• Collagen (metabolism)
• Diet, High-Fat (adverse effects)
• Elastin (metabolism)
• Interleukin-6 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Membrane Glycoproteins (deficiency, genetics)
• Mice
• Mice, Inbred C57BL
• Toll-Like Receptor 7 (deficiency, genetics)