PROTEOMICS BASED FUNCTIONAL CHAR OF MACROPHAGE SMOOTH MUSCLE CELL INTERACTIONS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在涉及血管壁的慢性炎症疾病状态（如动脉粥样硬化、动脉瘤、巨细胞动脉炎）中，浸润的单核细胞分化为组织破坏性巨噬细胞，在病理上重塑周围的细胞外基质（Galis和Khatri, 2002; Ross, 1999）。巨噬细胞可以通过调动复杂的蛋白水解酶和/或通过向周围血管平滑肌细胞发出信号来调动自身的基质破坏系统，从而直接介导这些作用。在这些巨噬细胞依赖的过程中，巨噬细胞和血管平滑肌细胞表达的促炎分泌因子的补体仍然是猜测的主题。利用体外模型，我们开发了一个完整的细胞系统，其中巨噬细胞和平滑肌细胞可以被触发表达与体内观察到的基质破坏表型相似，如果不是完全相同的话（Reddy et al, 1995; Punturieri et al, 2000）。利用蛋白质组学技术，我们将在本提案的支持下发展，寻求识别那些调节巨噬细胞分化和平滑肌细胞功能的分泌因子，以开发新的疾病活性生物标志物以及治疗干预的新靶点。

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.