Grant: Operating Grant

Cardiovascular diseases (CVD) are common among people with autoimmune diseases with arthritic symptoms. People affected by rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have a greater risk of early subclinical atherosclerotic disease due to accelerated development of atheromatous plaques. Biologically active lipids such as lysophosphatidic acid (LPA), play a role in RA pathophysiology. In particular, high levels of autotaxin (ATX), the enzyme that produces LPA, were detected in synovial fluids and sera from RA patients compared to osteoarthritis patients. LPA levels in synovial fluid and expression of several LPA receptors in the RA articular tissue were also increased. To date no research team has paid attention to elevated plasma levels of ATX in arthritis. Upon activation, platelets can shed minuscule particles, named microparticles. Elevated levels of platelet-derived microparticles are associated with many diseases state including RA and SLE. Since ATX can bind to activated platelets we monitored the presence of platelet-derived microparticles positive for ATX and discovered a new class of microparticles abundant in plasma from SLE patients but not from healthy individuals, the ATX-associated microparticles was identified. According to our hypothesis microparticles serve as a vehicle to transport ATX into the vascular wall, thereby disseminating inflammation within the vascular tissue. The main goal of the research proposal is to characterize and study the role of these microparticles-associated ATX in RA and SLE. The abundance of these microparticles might correlate with development of atherosclerosis and may become useful clinical marker for increased risk of CVD in arthritis.