TLR3 deficiency protects against collagen degradation and medial destruction in murine atherosclerotic plaques.
TLR3 deficiency protects against collagen degradation and medial destruction in murine atherosclerotic plaques.
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DOI：
10.1016/j.atherosclerosis.2013.03.035
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发表时间：
2013-07
期刊：
影响因子：
5.3
通讯作者：
Welch, Carrie L.
中科院分区：
文献类型：
--
作者：
Ishibashi, Minako;Sayers, Scott;D'Armiento, Jeanine M.;Tall, Alan R.;Welch, Carrie L.
Inflammatory cell activation plays a key role in atherosclerotic plaque growth and acute complications. While secretion of proteases and inflammatory cytokines are likely involved in the development of plaque instability, the precise mechanistic pathways are not well understood. Based on our previous study, we crossed Toll-like receptor 3 (Tlr3)−/− mice with a unique BALB-Apoe−/−Npc1−/− plaque complication-susceptible mouse model, as well as the widely-used B6-Ldlr−/− atherosclerosis model, to test the role of TLR3 signaling in the development of plaque instability. TLR3-deficient mice showed no change in aortic root lesion area, but displayed a marked increase in collagen and smooth muscle cell (SMC) content of lesions. Notably, Apoe−/−Npc1−/−Tlr3−/− mice exhibited a 50% reduction in the incidence of medial destruction, a precursor to aortic aneurysm formation. MMP-2 activity was markedly reduced in aortic extracts from Apoe−/−Npc1−/−Tlr3−/− compared to controls, while both MMP-2 and -9 activities were reduced in Ldlr−/−Tlr3−/− extracts. Consistent with the in vivo data, TLR3 deficiency suppressed MMP-2 activity induced by TNF-α or polyinosine–polycytidylic acid in macrophages from Apoe−/−Npc1−/− mice. TLR3 plays a critical role in regulating the degradation of extracellular matrix in lesions, in part by modulation of macrophage MMP-2 and -9 activities.
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影响因子：
15.9
作者：
Mullick, AE;Tobias, PS;Curtiss, LK
通讯作者：
Curtiss, LK
DOI：
10.1073/pnas.0506201102
发表时间：
2005-10-25
影响因子：
11.1
作者：
Johnson, JL;George, SJ;Jackson, CL
通讯作者：
Jackson, CL
影响因子：
15.9
作者：
Longo, GM;Xiong, WF;Baxter, BT
通讯作者：
Baxter, BT
影响因子：
4.6
作者：
Lin, Meng-Liang;Lu, Yao-Cheng;Chen, Shih-Shun
通讯作者：
Chen, Shih-Shun
DOI：
10.1161/01.atv.0000218496.60097.e0
发表时间：
2006-05-01
影响因子：
8.7
作者：
Kuzuya, M;Nakamura, K;Iguchi, A
通讯作者：
Iguchi, A