ROLE OF LIPOTPROTEINS IN THE TRANSPORT AND ACTIO OF OXYLIPINS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project answers the question "do lipoproteins transport lipid signals in the form of oxygenated FAs?" The projects extends on our previous finding that oxygenated FAs, or oxylipins, are acylated into lipoprotein lipids. Oxylipins are powerful lipid mediators of inflamation and so may be active agents of the well known lipoprotein induced inflammation. If so, understanding the role of lipoprotein-oxylipins in inflammation would give insight into the development of atherosclerosis and cardiovascular disease. The first aim investigates whether the lipoprotein-oxylipins are derived from autoxidation or enzymatically by combining treatment that modulate the activity of oxylipin-producing enzymes (e.g. COX, LOX and CYP) with treatments that modulate inflammation (e.g. LPS). The second aim asks whether presence of lipoprotein-oxylipins have any important biological effects using two surrogate endpoints for cardiovascular disease: endothelial cell polarity (a makrer for endothelial dysfunction) and cardiac fibroblast production of collagen (a marker for cardiac fibrosis).