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.
