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. SLE increases the risk of cardiovascular disease (CVD). The PI has found an increase in circulating endothelial cells (CEC) and a circulating form of a receptor for Protein C (EPCR), an anti-thrombotic and anti-inflammatory factor on endothelial cells. The hypothesis is that in SLE patients these CEC and PCR in plasma are related mechanistically to the increased CVD risk, as they reflect endothelial injury. Other hypotheses are that there is a specific protease that releases EPCR, which the investigators will try to identify, and that a gene variation in EPCR is related to CVD risk, particularly in patients with SLE. The study's aims are as follows: 1) Assess coronary artery disease (CAD) by ultrasound of carotid artery to measure intimal-medial thickness (IMT) and focal plaques. 2) Identify endothelial cell proteases that shed EPCR in TNF-alpha/IFN-gamma-stimulated human aortic endothelial cells (HAEC) and characterize its potential as a target using microarray and RNA interference. 3) Examine the frequency of elevated polymorphisms involving EPCR in SLE. SLE is a serious and relatively common disease, with multiorgan pathology, including the cardiovascular system. If CEC and EPCR prove to be markers of risk as well as mechanistic factors, these would be quite significant.
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