Angiotensin, the Vascular Endothelium, and Fibrinolysis - The Effects of PAI-1 Transcriptional Regulation on Human Monocyte Function

The discovery and subsequent application of small interfering RNA (siRNA) methods to achieve individual gene silencing in mammalian cells is a robust method that is well-described and validated in mammalian cell culture systems. We will apply this technique to achieve post-transcriptional "silencing" of PAI-1 in monocytes obtained from otherwise healthy volunteers, and study the subsequent loss of this gene's function on the migratory capacity of these cells in the proposed in vitro experimental system. This concept has not yet been demonstrated in the literature, and if validated, would be a novel and fundamental description of the role of PAI-1 in human monocyte biology as related to the development of atherosclerosis.