Psychological stress increases expression of aortic plaque inter- cellular adhesion molecule-1 and serum inflammatory cytokines in atherosclerotic rabbit model

Backgroud and objective Plaque rupture, platelet aggregation, and thrombogenesis are the main mechanisms of acute coronary syndrome (ACS), and inflammation factors play key roles in plaque unstability. Psychological stress promotes acute inflammatory response, leading to increased circulating levels of C-reactive protein (CRP), IL-6, and serum intercellular adhesion molecule (sICAM)1. But it is not clear that whether psychological stress has a direct effect on atherosclerotic plaque stability. The purpose of this study was to investigate effects of chronic psychological stress on inflammatory marker (ICAM-1) in atherosclerotic plaque, and inflammatory markers in peripheral blood. Materials and methods Sixty male rabbits were randomized into 2 groups: the control group (n =10) and the atherosclerotic group (n =50). The latter were fed on high fatty diet and were given a large dose of vitamin D3 (3 600 000IU/kg) via intraperitoneal injection. After 8 weeks, the atherosclerotic model was estaslished. Then the 50 atherosclerotic model rabbits were divided into 3 subgroups: no-stress subgroup (n =16), physiological stress subgroup (n =16) and psychological stress subgroup (n =18). In physiological stress subgroup and psychological stress subgroup, drinking was cut from twice a day to once a day. At the same time, psychological stress subgroup was given empty bottle stress, and this process lasted for 2 weeks. One hour after the last stress, the blood samples were collected and the serum levels of CRP, IL-6 amd ICAM-1 were tested by radioimmunoassay or enzyme linked immunosorbent assay. The aorta and heart were extracted for pathology examination, and the express of ICAM1 was tested by immunohistochemical examination. Results (1) After effective atherosclerotic animal model construction, the expression of ICAM-1 in aorta was higher in atherosclerotic group than that in control group (P<0.01), and was notably higher in psychological stress subgroup than that in no-stress subgroup or in physiological stress subgroup (2.18±0.17 vs 1.58±0.22, 1.22±0.15, P<0.001, respectively). The expression in physiological stress subgroup was higher than that in no-stress subgroup (58±0.22 vs 1.22±0.15, P=0.001). (2) The serum level of IL-6 (51.80±4.60 pg/ml vs 27.60±4.19 pg/ml,8.01±1.39 pg/ml,7.83±1.37 pg/ml), sICAM1(1.24±0.25 vs 0.85±0.09, 0.62±0.17, 0.57±0.11), CRP (1.00±0.37 vs 0.90±0.29,1.01±0.22, 0.71±0.13) in psychological stress group were significantly higher than that in other groups (All P<0.05). There was a positive relationship between the serum level of CRP, IL-6 and ICAM-1 and the expression of ICAM-1 in aorta wall ( r =0.59, r =0.75, r =0.87, P<0.01, respectively). Conclusions Psychological stress induces an increased expression of ICAM-1 in aortic atherosclerotic plaque, a higher serum level of CRP, IL-6, and sICAM-1 expression. Psychologial stress has a direct effect on the transition from stability to unstability through in-plaque and outplaque inflammation. The serum level of CRP, IL-6 and ICAM-1 can reflex the inflammatory degree in atherosclerotic plaque. (J Geriatr Cardiol 2008; 5:235-242)