title: TLR4/NF-κB signaling contributes to chronic unpredictable mild stress-induced atherosclerosis in ApoE-/- mice.
abstract: OBJECTIVE
  Chronic stress is an important risk factor for atherosclerotic diseases. Our previous studies have shown that chronic unpredictable mild stress (CUMS) accelerates atherosclerosis and up-regulates TLR4/NF-κB expression in apoE-/- mice. However, TLR4/NF-κB signaling whether directly contributes to the development of atherosclerosis in CUMS mice is unclear. We hypothesized that the interference of TLR4/NF-κB can ameliorate CUMS-induced inflammation and atherosclerosis in apoE-/- mice.
  
  
  METHODS
  ApoE-/- mice were exposed to 12 weeks CUMS. Ad-siRNA TLR4 was given by tail vein injection (10 μl/mouse, every 5 days), and PDTC (an inhibitor of NF-κB) was given by intraperitoneal injection (60 mg/kg, once a day). Plasma corticosterone concentrations were determined by solid-phase 125I radioimmunoassay. Atherosclerosis lesions in aortic sinuses were evaluated and quantified by IMAGEPRO PLUS. Western blotting was used to detect the expression of TLR4, NF-κB, and IL-1β in aortas of the mice. Plasma lipid profiles, IL-1β, TNF-α, and MCP-1 were measured by ELISA.
  
  
  RESULTS
  Our results indicated that CUMS apoE-/- mice treatment with siRNA TLR4 significantly decreased atherosclerosis and down-regulated TLR4, NF-κB, and inflammatory cytokines. PDTC also remarkably reduced atherosclerosis and the levels of IL-1β, TNF-α and MCP-1 in plasma. However, Treatment with siRNA TLR4 or PDTC had no effect on plasma corticosterone levels, and lipid profiles.
  
  
  CONCLUSIONS
  TLR4/NF-κB pathway may participate in CUMS-induced atherosclerosis through activation of proinflammatory cytokines in apoE-/- mice. Our data may provide a new potential therapeutic target for prevention of CUMS -induced atherosclerosis.
authors: Key Lab for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, 421001, People's Republic of China.
authors: Ya Ling
authors: YL
authors: Tang
authors: Chuanshan College, University of South China, Hengyang, 421001, People's Republic of China.
authors: Jian Hong
authors: JH
authors: Jiang
authors: Key Lab for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, 421001, People's Republic of China.
authors: Shuang
authors: S
authors: Wang
authors: Chuanshan College, University of South China, Hengyang, 421001, People's Republic of China.
authors: Zhu
authors: Z
authors: Liu
authors: Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, 421001, People's Republic of China.
authors: Xiao Qing
authors: XQ
authors: Tang
authors: Key Lab for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, 421001, People's Republic of China.
authors: Juan
authors: J
authors: Peng
authors: Key Lab for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, 421001, People's Republic of China.
authors: Yong-Zong
authors: YZ
authors: Yang
authors: Key Lab for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, 421001, People's Republic of China; Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, 421001, People's Republic of China.
authors: Hong-Feng
authors: HF
authors: Gu
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013312:Stress, Physiological; D013859:Thiocarbamates / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids; D016328:NF-kappa B; D034741:RNA, Small Interfering; D013859:Thiocarbamates; D051197:Toll-Like Receptor 4; C066229:prolinedithiocarbamate; D011392:Proline; D003345:Corticosterone