The effects of oxLDL and IFN-gamma-activated tissue resident cells on the progression of atherosclerosis and a proposed model for mast cell migration.

摘要

Atherosclerosis is a major problem today in the United States where cardiovascular disease is one of the leading causes of death in Americans. The chronic, inflammatory nature of Atherosclerosis results in the build-up of undetectable plaque that can eventually detach and cause heart attacks and strokes. When blood LDL concentration is high, LDL embeds in the arterial wall and is modified by nearby cells to an oxidized form, oxLDL. Endothelial cells express adhesion molecules that initiate monocyte adhesion, transmigration, and differentiation to macrophages. These macrophages along with other cells of the immune system play a significant role in the progression of this disease. Our lab has shown how TNF-alpha released by macrophages and Histamine released by mast cells act synergistically with oxLDL to increase monocyte adhesion.;In this study, we investigated the role of both oxLDL and IFN-gamma activated macrophages and mast cells by utilizing a static assay. IFN-gamma is predominantly released by Th1 cells and is a potent polarizing agent for macrophages. The static assay consists of a bed of endothelial cells that are activated by mediators released by oxLDL and IFN-gamma activated macrophages and mast cells. The adhesion capabilities of monocytes was used to both quantify and qualify the data. These experiments may provide incite as to how to further the investigation in the future. The next area we were interested in exploring was to create a model for mast cell migration. Mast cells exist in small numbers in the blood vessel, but exist in elevated amounts in both the blood vessel and around plaque. We have created a general model that still requires investigation.