MECHANISMS OF AGEPC ACTION ON VASCULAR ENDOHELIUM

拟议的研究计划将集中在乙酰甘油的作用上。 乙醚磷胆碱(AGEPC，血小板激活因子)，一种有效的 血管活性/炎症介质对血管内钙稳态的影响 内皮细胞。AGEPC特异性效应的生化和细胞机制 钙运动(45Ca~(2+)通量)和细胞内游离钙的研究 将研究浓度(Quin 2，钙敏感荧光染料) 从不同血管类型分离的培养内皮细胞中 物种。 具体目标包括：1)定义时间和 AGEPC诱导内皮细胞改变的浓度依赖模式 钙动态平衡；2)确定细胞的源和汇 钙参与AGEPC的作用；3)激动剂诱导的特征 AGEPC效应的脱敏及AGEPC的相互作用 和其他血管活性/炎症物质在内皮细胞钙中 动态平衡；4)确定不同的钙拮抗剂在 该系统；以及5)检测环核苷酸(环AMP， 环鸟苷酸)和环氧合酶产物(前列环素) 钙稳态。这些研究应该会提供有关 AGEPC对血管内皮细胞作用的细胞机制 与急性和慢性炎症有关。此外，这些研究可能 也为改变内皮细胞钙的作用提供了新的见解 在更复杂的血管疾病的发病机制中的动态平衡，如 血栓形成和动脉粥样硬化。

The proposed research plan will focus on the action of acetyl glyceryl ether phosphorylcholine (AGEPC, platelet activating factor), a potent vasoactive/inflammatory mediator, on calcium homeostasis in vascular endothelium. Biochemical and cellular mechanisms of AGEPC-specific effects on calcium movements (45Ca2+ flux) and on cytosolic free calcium concentration (quin 2, calcium-sensitive fluorescent dye) will be studied in cultured endothelial cells isolated from different vessel types and species. Specific aims include: 1) defining the temporal- and concentration-dependent patterns of AGEPC-induced changes in endothelial calcium homeostasis; 2) identifying the sources and sinks of cellular calcium involved in the action of AGEPC; 3) characterizing agonist-induced desensitization of AGEPC effects and the potential interactions of AGEPC and other vasoactive/inflammatory substances in endothelial calcium homeostasis; 4) defining the effects of different calcium antagonists in this system; and 5) examining the role of cyclic nucleotides (cyclic AMP, cyclic GMP) and cyclooxygenase products (prostacyclin) in endothelial calcium homeostasis. These studies should provide new information on the cellular mechanisms of AGEPC action on vascular endothelium, a process relevant to acute and chronic inflammation. In addition, these studies may also provide new insights into the role of altered endothelial calcium homeostasis in the pathogenesis of more complex vascular diseases, such as thrombosis and atherosclerosis.