Defining the regulation of oxLDL-mediated tissue factor induction in human monocytes. (2014)

Undergraduate: Ben Jepson

Faculty Advisor: Nigel Mackman
Department: Biology

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Atherosclerosis is one of the leading causes of death in the United States and is responsible for nearly 75% of cardiovascular related deaths. A primary contributing factor to atherosclerosis formation is a diet rich in fat and cholesterol. Work in the Mackman lab has provided support for the hypothesis that a form of LDL (oxLDL) induces a hypercoagulable state by up-regulating a protein Tissue Factor (TF). The goal of my SURF study was to determine the regulatory pathways by which oxLDL leads to induction of TF gene expression in monocytic cells. A series of 24-hour time courses were performed on human THP-1 cells (human leukemia monocytic cells) to determine the increase in TF expression. Bacterial lipopolysaccharide (LPS) was used as a positive control since the pathways that lead to the induction of TF gene expression in monocytes are well established. The transcription factors involved include NF-KB, AP1 and Egr-1. As expected from previous studies, LPS induced a transient increase in TF mRNA expression with a peak at 6 hours. OxLDL stimulated a time dependent increase in TF mRNA expression that peaked at 24 hours. Although both LPS and oxLDL activated the TLR4 receptor, the differences in the kinetics of TF mRNA expression with the two agonists suggest that oxLDL induces TF gene expression via different pathways.