Marcus A J, Hajjar D P
Thrombosis Research Laboratory, New York Veterans Affairs Medical Center, NY.
J Lipid Res. 1993 Dec;34(12):2017-31.
Thus, it is apparent that humoral factors released during inflammation can affect cholesterol metabolism in arterial cells during atherogenesis. These humoral factors released from the macrophage, endothelium, or smooth muscle can modify the cytokine/growth factor/eicosanoid network in the vessel wall in either a paracrine or autocrine manner (6, 40). We also postulate that this could result in alterations in native LDL induced by endothelium (6, 40). Therefore, regulation of the cytokine/growth factor network by eicosanoids may represent an important aspect of arterial responsiveness to injury, as well as progression of intimal hyperplasia and CE deposition in a setting of inflammatory cell activation. Recent understanding of the biochemistry of eicosanoids and the metabolic consequences of these biological response modifiers has helped us to further develop this concept as it relates to mechanisms involving cholesterol delivery and trafficking within the vessel wall during thrombo-atherosclerosis. In this review, we have attempted to highlight recent data which support our classification system for cell-cell interactions, and document that eicosanoids and cytokines released from one cell can activate corresponding receptors on neighboring cells. They can interact with each other in this "cross talk" phenomenon during transmembrane signaling. Recent evidence demonstrating that phosphorylation reactions involving protein kinases A and C and tyrosine protein kinase, coupled with the highly regulated eicosanoid pathway and the DAG-phosphatidylinositol system, appears to have a major impact in our understanding of at least three processes related to atherogenesis: 1) cholesterol delivery, 2) intracellular cholesterol processing, and 3) cholesterol efflux. Identification of these diverse pathways associated with transmembrane signaling have helped us to define processes related to thrombosis since they share common pathways in a complex arteriopathy during atherogenesis.
因此，很明显，炎症过程中释放的体液因子可在动脉粥样硬化形成过程中影响动脉细胞中的胆固醇代谢。这些从巨噬细胞、内皮细胞或平滑肌释放的体液因子可以旁分泌或自分泌的方式改变血管壁中的细胞因子/生长因子/类花生酸网络（6, 40）。我们还推测，这可能导致内皮诱导的天然低密度脂蛋白发生改变（6, 40）。因此，类花生酸对细胞因子/生长因子网络的调节可能代表了动脉对损伤的反应以及内膜增生和胆固醇酯沉积在炎症细胞激活情况下进展的一个重要方面。最近对类花生酸生物化学及其作为生物反应调节剂的代谢后果的理解，有助于我们进一步发展这一概念，因为它涉及血栓性动脉粥样硬化过程中血管壁内胆固醇递送和转运的机制。在这篇综述中，我们试图强调支持我们细胞间相互作用分类系统的最新数据，并证明从一个细胞释放的类花生酸和细胞因子可以激活相邻细胞上的相应受体。在跨膜信号传导过程中，它们可以在这种“串扰”现象中相互作用。最近的证据表明，涉及蛋白激酶A、C和酪氨酸蛋白激酶的磷酸化反应，再加上高度调节的类花生酸途径和二酰甘油 - 磷脂酰肌醇系统，似乎对我们理解至少三个与动脉粥样硬化相关的过程有重大影响：1）胆固醇递送，2）细胞内胆固醇处理，3）胆固醇流出。鉴定与跨膜信号传导相关的这些不同途径有助于我们定义与血栓形成相关的过程，因为它们在动脉粥样硬化形成过程中的复杂动脉病变中共享共同途径。
