Research Focus

Research activities: Inflammatory Components of Atherosclerosis

Occupants of the Curtiss laboratory study plasma lipoproteins, atherosclerosis and inflammation. The laboratory makes specific use of molecular biology, animal models of atherosclerosis, and plasma lipoprotein and lipid biochemistry to identify mechanisms involved in protection against atherosclerosis and cardiovascular disease. Structure and function relationships of plasma apolipoprotein (apo) A-I are being explored using monoclonal antibodies, genetic mutants of apo A-I and reconstituted populations of high density lipoproteins (HDL). These tools are used to identify how apo A-I and HDL participate in activation of the plasma cholesterol esterification enzyme (LCAT) and in cellular cholesterol efflux. Studies of apo E involve identification of its role in the inflammatory components of atherosclerosis. Using bone marrow transplantation we are examining the effects of macrophage expression of apo E in atherosclerosis-prone transgenic mice including apo E-deficient, apo A-I deficient and the LDL-receptor deficient mice. The role of specific cytokines such as IL-8 and interferon gamma in the chronic inflammation of atherosclerosis also are being identified.

Education

B.S., University of Washington
M.A., University of Colorado at Boulder
Ph.D., University of Washington

Awards & Professional Activities

Curtiss, L.K., Member, Atherosclerosis and Inflammation in the Cardiovascular Sciences Study Section, National Institutes of Health; Associate Editor, Journal of Lipid Research; Editorial Boards, Arteriosclerosis, Thrombosis and Vascular Biology

Selected References

Lee, C. H., Chawla, A., Urbiztondo, N., Liao, D., Boisvert, W. A., Evans, R. M. and Curtiss, L. K. Transcriptional repression of atherogenic inflammation: Modulation by PPARdelta. Science 302:453-457. Erratum in Science, Nov. 14, 302:1153, 2003.

Schiller, N.K., Black, A.S., Bradshaw, G.P., Bonnet, D.J., and Curtiss, L.K. Participation of macrophages in atherosclerotic lesion morphology in LDLr-/- mice. J. Lipid Res., 45:1398-1409, 2004.

Binder, C.J., Hartvigsen, K., Chang, M.K., Miller, M., Broide, D., Palinski, W., Curtiss, L.K., Corr, M., and Witztum, J.L. IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis. J. Clin Invest., 114:317-319, 2004.

Wiedmer, T., Zhao, J., Li, L., Zhou, Q., Hevener, A., Olefsky, J.M., Curtiss, L.K., and Sims, P.J. Adiposity, dyslipidemia and insulin resistance in mice with targeted deletion of phospholipid scramblase 3 (PLSCR3). Proc. Natl. Acad. Sci., 101:13296-13301, 2004.