PROTEOMICS BASED FUNCTIONAL CHAR OF MACROPHAGE SMOOTH MUSCLE CELL INTERACTIONS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In chronic inflammatory disease states involving the blood vessel wall (e.g., atherosclerosis, aneurysm, giant cell arteritis), infiltrating monocytes differentiate into tissue-destructive macrophages that pathologically remodel the surrounding extracellular matrix (Galis and Khatri, 2002; Ross, 1999). Macrophages can mediate these effects directly by mobilizing a complex mix of proteolytic enzymes and/or by signaling surrounding vascular smooth muscle cells to mobilize their own repertories of matrix-destructive systems. In either of these macrophage-dependent processes, the complement of pro-inflammatory secreted factors expressed by macrophages and vascular smooth muscle cells remain the subject of conjecture. Using in vitro models, we have developed an intact cell system wherein macrophages and smooth muscle cells can be triggered to express matrix-destructive phenotypes similar, if not identical, to that observed in vivo (Reddy et al, 1995; Punturieri et al, 2000). Taking advantage of proteomic techniques that will be developed under the auspices of this proposal, we seek to identify those secreted factors that regulate macrophage differentiation and smooth muscle cell function for the purpose of developing new biomarkers of disease activity as well as novel targets for therapeutic intervention.