Interleukin 18 and Atherosclerosis during Stress

说明(申请人提供)：白介素18(IL-18)是一种促炎细胞因子，具有促动脉粥样硬化的特性，其水平可通过心理应激而升高。由于应激导致动脉粥样硬化，我们推测IL-18是动脉粥样硬化应激依赖发展的介质之一。为了验证这一假设，我们将使用易患动脉粥样硬化的小鼠的载脂蛋白E缺失(ApoE-/-)和小鼠的载脂蛋白E和IL-18缺失(ApoE-/-IL-18-/-)。APOE-/-和ApoE-/-IL-18-/-小鼠将被分成两组，一组接受应激，另一组不受干扰。应激和IL-18对动脉粥样硬化的影响将通过以下方面来评估：1.含有病变的主动脉的百分比；2.病变的形态计量学分析；3.病变的组织化学分析；4.应激相关或IL-18诱导的促动脉粥样硬化分子的水平。这些实验将确定IL-18是否是在应激过程中介导动脉粥样硬化的重要因素。如果是这样的话，IL-18是减少应激对动脉粥样硬化影响的靶点。

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.