Characterization of CXCL 16 in atherosclerosis

J. David Gladstone Institutes, San Francisco CA

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Abstract

DESCRIPTION (provided by applicant): The objective of this proposal is to more fully understand the roles of chemokines and scavenger receptors in atherogenesis. Chemokines and scavenger receptors mediate processes crucial to the early formation of the atherosclerotic lesion. CXCL16, a recently identified chemokine that mediates the chemotaxis of activated T cells, also binds and internalizes oxidized low density lipoproteins (OxLDL). CXCL16 exists as a membrane-bound protein similar in structure to the chemokine fractalkine, in vitro assays will be used to define the OxLDL binding domains of CXCL16, and compare this activity to fractalkine. Also, the progression of atherosclerosis will be measured in CXCL16 knockout mice. This data will determine if CXCL16 is a critical factor in atherogenesis in vivo, providing important insights into the roles of chemokines and scavenger receptors in this disease model.