MCRC Project 2 - PI Ramsey-Goldman
CURRENT MCRC PROJECT
SOLVABLE: Study of Lupus Vascular and Bone Long-term Endpoints
Why are we doing this study?
Systemic lupus erythematosus (SLE, lupus) is the prototypic systemic inflammatory autoimmune disease that affects predominantly young, premenopausal women. As clinicians, we are seeing increasing numbers of young women with SLE experiencing cardiovascular events, stroke and myocardial infarction, as well as the complication of osteoporosis, fractures. The role of inflammation in atherosclerosis and osteoporosis may be particularly relevant in explaining why SLE women are affected by these complications at such an early age. Monocytes and macrophages play an essential role in the initiation and progression of atherosclerosis and osteoporosis. This project merges discoveries identified in the laboratory of Dr. Richard Pope on the differential gene expression profiles between monocytes and macrophages with longitudinal observations of the SOLVABLE cohort, defining epidemiological outcomes of women with SLE by Dr. Rosalind Ramsey-Goldman. The current approach allows us to determine if SLE patients with early evidence of atherosclerosis or osteoporosis demonstrate differences in genes important to the pathogenesis of these disorders, when macrophage differentiation proceeds in an unbiased environment.
What we are we doing in this study?
Innovative aspects of this study are to monitor progression of subclinical cardiovascular disease with serial measurements of imaging after controlling for covariates such as medication use and immune/inflammatory markers (aim 1) and simultaneously harvest RNA from monocytes and macrophages for gene expression profiles (aims 2 and 3). Our overriding hypothesis is that the increased occurrence and progression of cardiovascular and osteoporosis subclinical markers and/or event outcomes in women with SLE are associated with differential gene expression profiles of selected biological pathways in monocytes and macrophages. This study represents a continuation from our study supported through two MCRC funding cycles.
MCRC Project #2, SOLVABLE is the center piece for the Clinical Lupus Research Program at Northwestern University.