Grant: Operating Grant

The formation of platelet-monocyte aggregates is a known early marker of cardiovascular disease, which if untreated can lead to stroke or heart attack, and ultimately to death. Recent evidence suggests that platelet-monocyte aggregates also play a direct functional role in these processes. Our knowledge on these aggregates is limited, however. Having a detailed understanding of how they are formed, and how they interact with the surface of blood vessels to elicit their deleterious physiological effects, is critical for our ability to design appropriate measures for prevention or treatment. Proteomics is a new, high-throughput approach that aims at providing a comprehensive analysis of all of the proteins in a biological system. Owing to recent technical advances, it can now routinely identify hundreds, or even thousands of proteins that are present in cells and tissues, and detect and quantify any changes they may undergo. We propose to use proteomics to identify the proteins that are involved in platelet-monocyte aggregate formation and function, determine the changes platelets, monocytes, and cells lining the blood vessels undergo, and establish the exact sequence of these evenets. Such information is particularly helpful as it can be used to develop and test intervention strategies to block or counter these events. We are uniquely qualified to carry out the proposed research, as we have the necessary equipment, experience, and track record of success for each aspect of the proposal.