Interleukin 18 and Atherosclerosis during Stress

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DESCRIPTION (provided by applicant): Interleukin 18 (IL-18) is a pro-inflammatory cytokine with pro-atherogenic properties whose level can be elevated by psychological stress. Since stress contributes to atherosclerosis we hypothesized that IL-18 is one of the mediators of the stress- dependent development of atherosclerosis. To test this hypothesis we will use the atherosclerosis prone mice null for Apolipoprotein E (ApoE-/-) and in mice null for mice Apolipoprotein E and IL-18 (ApoE-/- IL-18-/-). ApoE-/- and ApoE-/- IL-18-/- mice will be divided in two groups, one receiving stress and one will be left undisturbed. The effects of stress and of IL-18 on atherosclerosis will be evaluated by investigating: 1. the percentage of aorta containing lesions; 2. the morphometric analysis of the lesions; 3. the histochemical analysis of the lesions; 4. the level of stress-related or IL-18 induced pro-atherogenic molecules. These experiments will determine whether IL-18 is an important factor in mediating atherosclerosis during stress. If so, IL-18 is a target for reducing the effects of stress on atherosclerosis.