Interleukin 18 and Atherosclerosis during Stress

描述（由申请人提供）：白细胞介素18（IL-18）是一种具有促动脉粥样硬化特性的促炎细胞因子，其水平可因心理应激而升高。由于应激导致动脉粥样硬化，我们假设IL-18是动脉粥样硬化应激依赖性发展的介质之一。为了检验这一假设，我们将使用载脂蛋白E无效的动脉粥样硬化倾向小鼠（ApoE-/-）和载脂蛋白E和IL-18无效的小鼠（ApoE-/- IL-18-/-）。将ApoE-/-和ApoE-/- IL-18-/-小鼠分成两组，一组接受应激，另一组不受干扰。通过以下研究评价应激和IL-18对动脉粥样硬化的影响：1.含病变主动脉的百分比; 2.病变的形态计量学分析; 3.病变组织化学分析; 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是否是介导应激期间动脉粥样硬化的重要因素。如果是这样的话，IL-18是减少压力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.