Repeated exposure to stressors do not accelerate atherosclerosis in ApoE−/− mice


      Psychosocial stress is suggested to play a significant role in development of cardiovascular disease. To evaluate the effects of repeated exposure to stress on atherosclerosis in atherosclerosis-prone ApoE−/− mice we used five different stressors. We further sought to determine whether stress combined with high salt diet induces dysfunctional neurohormonal regulation and impaired salt excretion, thus amplifying the atherogenic potential of salt. The five stressors were evaluated in male C57BL/6 mice and ApoE−/− mice (studies I and II) and then used in female ApoE−/− mice to study their effect on atherosclerosis (study III). The mice in study III received standard or high salt diet (8%) alone or in combination with stress for 12 weeks. Urine and plasma were collected for corticosterone and lipid analysis, respectively. Acute blood pressure (BP) and heart rate (HR) responses to stress were measured using telemetry. Plaque burden was assessed in the thoracic aorta and aortic root. Plaque morphology was investigated regarding macrophages and collagen content. Urinary corticosterone chronically increased in stressed mice (P < 0.05 control vs. stress, P < 0.05 control salt vs. stress salt). BP and HR increased acutely during all stressors (P < 0.05). Body weight gain decreased significantly in the stress group (P < 0.05 vs. control). However, stress did not alter plasma lipid levels, plaque area or plaque morphology. Increased BP and HR suggest an acute stress-related response in ApoE−/− mice. Furthermore, stress chronically decreased body weight gain and increased urinary corticosterone levels. Notably, despite an apparent stress effect, stress affected neither atherogenesis nor plaque morphology.


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