title: Effects of emotional and physiological stress on plaque instability in apolipoprotein E knockout mice.
abstract: In the present study, we sought to investigate the effects of emotional and physiological stress on plaque instability in atherosclerosis. We used different stress-treated apolipoprotein E (ApoE)-deficient mice, which have been shown to spontaneously develop atherosclerosis with features similar to those seen in humans, as an animal model. Morphology study showed that emotional stress (ES) obviously promoted the development of atherosclerotic plaques and plaque instability evidenced by significantly increasing plaque size, plaque-to-surface ratio and plaque calcification, and enhancing the frequency of large necrotic core and medial erosion compared with control ApoE(-/-) mice (P<0.01). Physiological stress (PS) treatment alone did not affect the plaque stability compared with control ApoE(-/-) mice (P>0.05). However, the combination of ES and PS treatment (CS) initiated much stronger plaque instability compared with ES treatment alone (P<0.01), increased the frequency of thin fibrous caps, and even triggered plaque rupture and buried fibrous cap. Immunohistochemical analysis indicated that both ES and CS treatment led to an increase in the accumulation of macrophages and T cells and a decrease of smooth muscle cells, reflecting an unstable atherosclerotic plaque phenotype, in the atherosclerotic lesions in ApoE(-/-) mice. PS alone did not affect plaque cellular components. Similarly, CS-mediated changes in atherosclerotic plaque composition were stronger than that caused by ES alone (P<0.01). Taken together, ES treatment alone is sufficient to promote plaque instability. PS alone does not affect atherosclerotic plaque development, but can potentiate ES-mediated plaque destabilization.
authors.affiliation: Department of Cardiology, PLA General Hospital, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Zhai
authors.forename: Yundai
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Zhou
authors.forename: Junjie
authors.initials: J
authors.lastname: Yang
authors.forename: Hongbin
authors.initials: H
authors.lastname: Liu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001018:Aortic Diseases / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics*; D001835:Body Weight; D016122:Brachiocephalic Trunk / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism; D002114:Calcinosis / Q000473:pathology / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000503:physiopathology; D013312:Stress, Physiological; D013315:Stress, Psychological; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001057:Apolipoproteins E; D017252:CD3 Complex; D008055:Lipids; C081026:CD68 protein, mouse; D000097382:CD68 Molecule