PMID- 22428781 OWN - NLM STAT- MEDLINE DCOM- 20130521 LR - 20121211 IS - 1607-8888 (Electronic) IS - 1025-3890 (Linking) VI - 16 IP - 1 DP - 2013 Jan TI - Chronic psychological stress induces vascular inflammation in rabbits. PG - 87-98 LID - 10.3109/10253890.2012.676696 [doi] AB - Psychological stress is associated with a systemic inflammatory response. It is unclear, however, whether psychological stress contributes to vascular inflammation. Here, we examined the effects of unpredictable chronic mild stress (UCMS) on vascular inflammation in rabbits. One hundred rabbits were randomly divided into control and stress groups. UCMS was induced by a set of defined adverse conditions applied in a shuffled order for 4, 8, 12, or 16 weeks, and rabbits were killed 24 h after the end of the UCMS protocol. Expression of different inflammatory molecules was analyzed by real-time polymerase chain reaction, immunohistochemistry, or enzyme-linked immunosorbent assay. UCMS resulted in depression-like behaviors, decreased body weight gain, and hypertension with no significant effects on serum lipids. Aortic mRNA and protein expression for tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor, and expression of intercellular adhesion molecule-1 (ICAM-1) protein were increased. UCMS increased circulating concentrations of corticosterone, TNF-alpha, and CRP throughout. Moreover, stress downregulated the expression of endothelial nitric oxide synthase. At 16 weeks of UCMS, macrophage infiltration and lipid accumulation in the subendothelial space were detected in the aorta. In cultured murine vascular smooth muscle cells, treatment with serum from stressed rabbits significantly increased phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and upregulated expression of MCP-1 and ICAM-1 mRNAs, in which the effect was blunted by a TNF-alpha neutralizing antibody or p38 and JNK inhibitors. Our results indicate that chronic psychological stress induces vascular inflammation via TNF-alpha and p38/JNK pathways, which may contribute to the development of atherosclerosis. FAU - Lu, Xiao Ting AU - Lu XT AD - Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong Province, PR China. FAU - Liu, Yun Fang AU - Liu YF FAU - Zhao, Li AU - Zhao L FAU - Li, Wen Jing AU - Li WJ FAU - Yang, Rui Xue AU - Yang RX FAU - Yan, Fang Fang AU - Yan FF FAU - Zhao, Yu Xia AU - Zhao YX FAU - Jiang, Fan AU - Jiang F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120425 PL - England TA - Stress JT - Stress (Amsterdam, Netherlands) JID - 9617529 SB - IM MH - Animals MH - Behavior, Animal/physiology MH - Blotting, Western MH - Body Weight/physiology MH - Cells, Cultured MH - Chronic Disease MH - Eating/physiology MH - Hemodynamics/physiology MH - Homeostasis/physiology MH - Hypothalamo-Hypophyseal System/physiology MH - Immunohistochemistry MH - Lipid Metabolism/physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Myocytes, Smooth Muscle/physiology MH - Noise/adverse effects MH - Periodicity MH - Pituitary-Adrenal System/physiology MH - Rabbits MH - Real-Time Polymerase Chain Reaction MH - Restraint, Physical MH - Stress, Psychological/*complications/*pathology/psychology MH - Vasculitis/*etiology/*pathology EDAT- 2012/03/21 06:00 MHDA- 2013/05/23 06:00 CRDT- 2012/03/21 06:00 PHST- 2012/03/21 06:00 [entrez] PHST- 2012/03/21 06:00 [pubmed] PHST- 2013/05/23 06:00 [medline] AID - 10.3109/10253890.2012.676696 [doi] PST - ppublish SO - Stress. 2013 Jan;16(1):87-98. doi: 10.3109/10253890.2012.676696. Epub 2012 Apr 25.