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. The central hypothesis is that vacular PAI-1 excess promotes the development of intravascular thrombosis. We will test that secreted factors from adiocytes have autocrine, paracrine, and endocrine effects that have deleterious effect on the fibrinolytic system, either by enhancing PAI-1 production or impairing endothelial t-PA release.