Methods to identify therapeutic agents
AssigneeThe Scripps Research Institute
InventorPaul Wentworth
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Abstract
As illustrated herein, cholesterol is oxidized when it is present in atherosclerotic plaques. This reaction generates cholesterol oxidation or ozonation products that can act as chemotactic attractants of macrophages, can promote differentiation of monocytes into macrophages and can increase expression of E-selectin and Class A scavenger receptor (SR-A). The present application is directed to methods of using such cholesterol ozonation products to identify agents that can be used to treat atherosclerosis and other inflammatory artery diseases.
Claims16
A method for identifying an agent that can inhibit recruitment of macrophages to atherosclerotic tissues that comprises contacting a macrophage with a test agent and observing whether the macrophage migrates toward a source of cholesterol ozonolysis products 4a or 5a:
A method for identifying an agent that can inhibit atherosclerosis that comprises contacting an endothelial cell with a test agent and observing whether expression of E-selectin increases in the endothelial cell exposing the endothelial to cholesterol ozonolysis products 4a or 5a in the presence of LDL:
A method for identifying an agent that can inhibit monocyte differentiation into macrophages that comprises contacting a monocyte cell with a test agent and observing whether the monocyte differentiates into a macrophage, wherein the monocyte is cultured with cholesterol ozonolysis product 4a or 5a:
An isolated dansyl derivative of cholesterol ozonolysis product consisting essentially of compound 5d or 5e.
An isolated dansyl derivative of cholesterol consisting essentially of compound 9c or 9d.
Dependencies are inferred from the claim text.