PATHOBIOLOGY OF FOAM CELLS IN ATHEROSCLEROSIS

单核细胞从循环中迁移到内皮下 位置，以及它们随后转化为富含胆固醇酯的 泡沫细胞是最早发现的病变过程之一 阵 在拟议的实验中，巨噬细胞功能方面的思想 在血管生物学中发挥作用。 我们尤其 将研究巨噬细胞源性泡沫细胞的释放和/或激活 细胞外蛋白酶。 可溶性纤溶酶原激活物的分泌， 将测定膜相关激活剂的表达。 的 还将评估其它中性蛋白酶的活性，包括 胶原酶 除了巨噬细胞在结缔组织中的重要作用外， 组织降解和纤维蛋白溶解，巨噬细胞还激活蛋白酶 参与凝血。 因此，对促凝血剂的阐述 测定巨噬细胞衍生的泡沫细胞的活性。 利用 这些参数，细胞的激活状态与其 随后对脂质和/或脂蛋白积累反应将 研究了 最后，研究了可溶性泡沫细胞因子对 内皮细胞和平滑肌细胞的各种特性对 将研究血管稳态。 这些包括纤溶酶原 激活剂/抑制剂活性，胶原酶的释放， 细胞衍生基质，促凝血活性的表达和对 单核细胞 阐明巨噬细胞源性泡沫细胞如何直接 或间接促进或调节这些过程的其他细胞将 有助于我们理解病变进展。

The emigration of monocytes from the circulation to a subendothelial position, and their subsequent transformation into cholesteryl ester rich foam cells is one of the earliest recognizable processes in lesion formation. In proposed experiments, aspects of macrophage function thought to play a role in vascular biology will be assessed. In particular, we will investigate macrophage-derived foam cells' release and/or activation of extracellular proteases. Secretion of soluble plasminogen activator and expression of membrane associated activator will be determined. The activity of other neutral proteases will also be assessed including that of collagenase. In addition to the important role of macrophage in connective tissue degradation and fibrinolysis, macrophage also activate proteases involved in coagulation. Therefore, the elaboration of procoagulant activity by macrophage-derived foam cells will be determined. Utilizing these parameters, the relationship the cell's state of activation and its subsequent response to lipid and/or lipoprotein accumulation will be investigated. Finally, the effect of soluble foam cell factors on a variety of endothelial and smooth muscle cell properties important to vascular homeostasis will be investigated. These include plasminogen activator/inhibitor activities, release of collagenase, degradation of cell-derived matrix, expression of procoagulant activity and reactivity to monocytes. Elucidation of how macrophage-derived foam cells may directly or indirectly contribute to or modulate these processes by other cells will contribute significantly to our understanding of lesion progression.