title: Atherosclerotic plaque disruption induced by stress and lipopolysaccharide in apolipoprotein E knockout mice.
abstract: To establish an animal model with disruptions of atherosclerotic plaques, 96 male apolipoprotein E knockout (apoE(-/-)) mice were randomly divided into stress, lipopolysaccharide (LPS), stress+LPS, and control groups (n = 24 each). All mice were fed a high-fat diet throughout the experiment, and carotid atherosclerotic lesions were induced by placement of a constrictive perivascular collar. Four weeks after surgery, mice in the LPS and stress+LPS groups were intraperitoneally injected with LPS (1 mg/kg twice per week for 8 wk). Eight weeks after surgery, mice in the stress and stress+LPS groups were treated with intermittent physical stress (electric foot shock and noise stimulation) for 4 wk. Morphological analysis revealed a plaque disruption rate of 16.7% in control, 34.8% in LPS, 54.2% in stress, and 60.9% in stress+LPS groups. The disruption rates in stress and stress+LPS groups were both significantly higher than those of controls (P = 0.007 and P = 0.002, respectively). Luminal thrombosis secondary to plaque disruption was observed only in the stress+LPS group. Both stress and LPS stimulation significantly decreased fibrous cap thickness and increased macrophage and lipid contents in plaques. Moreover, the combination of stress and LPS stimulation further lowered cap thickness and enhanced accumulation of macrophages and expression of inflammatory cytokines and matrix metalloproteinases. Stress activated the sympathetic nervous system, as manifested by increased blood pressure and flow velocity. Plasma fibrinogen levels were remarkably elevated in the stress and stress+LPS groups. In conclusion, stress- and LPS-costimulated apoE(-/-) mice provide a useful model for studies of plaque vulnerability and interventions.
authors.affiliation: Shandong Univ. Qilu Hospital, No. 107, Wen Hua Xi Road, Jinan, Shandong 250012, P. R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ni
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Peng Fei
authors.initials: PF
authors.lastname: Zhang
authors.forename: Shi Fang
authors.initials: SF
authors.lastname: Ding
authors.forename: Chun Xi
authors.initials: CX
authors.lastname: Liu
authors.forename: Xiao Ling
authors.initials: XL
authors.lastname: Liu
authors.forename: Yu Xia
authors.initials: YX
authors.lastname: Zhao
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001777:Blood Coagulation; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D003250:Constriction; D016207:Cytokines / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000378:metabolism; D005355:Fibrosis; D006439:Hemodynamics; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008264:Macrophages / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009638:Norepinephrine / Q000097:blood; D012421:Rupture; D013315:Stress, Psychological / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D004041:Dietary Fats; D008070:Lipopolysaccharides; D005340:Fibrinogen; D020782:Matrix Metalloproteinases; D009638:Norepinephrine