PHAGOCYTE ENHANCEMENT THERAPY FOR ATHEROSCLEROSIS
First Claim
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1. A method for identifying an enhancer of phagocytic clearance of free cholesterol-induced (FC-induced) macrophages, the method comprising(a) labeling an FC-induced apoptotic macrophage;
- (b) culturing the FC-induced apoptotic macrophage in the presence of phagocytes and in the presence of a test compound, thereby providing a test sample; and
(c) determining the amount of a label present in the phagocytes in the test sample, wherein, an increase in the amount of the label in the phagocytes in the presence of the test compound compared to the amount of the label present in the phagocytes cultured with FC-induced apoptotic macrophages in the absence of the test compound indicates that the compound is an enhancer of phagocytic clearance of a FC-induced apoptotic macrophages.
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Abstract
Compounds that increase phagocytosis of apoptotic macrophages or necrotic cells that are associated with advanced atherosclerotic lesions are useful for treating atherosclerosis. Methods are provided for identifying such compounds and for preventing or treating atherosclerosis by increasing phagocytosis of apoptotic macrophages associated with advanced atherosclerotic lesions.
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Citations
41 Claims
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1. A method for identifying an enhancer of phagocytic clearance of free cholesterol-induced (FC-induced) macrophages, the method comprising
(a) labeling an FC-induced apoptotic macrophage; -
(b) culturing the FC-induced apoptotic macrophage in the presence of phagocytes and in the presence of a test compound, thereby providing a test sample; and (c) determining the amount of a label present in the phagocytes in the test sample, wherein, an increase in the amount of the label in the phagocytes in the presence of the test compound compared to the amount of the label present in the phagocytes cultured with FC-induced apoptotic macrophages in the absence of the test compound indicates that the compound is an enhancer of phagocytic clearance of a FC-induced apoptotic macrophages. - View Dependent Claims (5, 6, 7, 10, 13, 14, 15, 35, 39)
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2. A method for identifying an enhancer of phagocytic clearance of free cholesterol-induced (FC-induced) macrophages, the method comprising
(a) labeling an FC-induced necrotic macrophage; -
(b) culturing the FC-induced necrotic macrophage in the presence of phagocytes and in the presence of a test compound, thereby providing a test sample; and (c) determining the amount of a label present in the phagocytes in the test sample, wherein, an increase in the amount of the label in the phagocytes in the presence of the test compound compared to the amount of the label present in the phagocytes cultured with FC-induced necrotic macrophages in the absence of the test compound indicates that the compound is an enhancer of phagocytic clearance of a FC-induced necrotic macrophages. - View Dependent Claims (8, 9, 11, 12, 36, 40)
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3. A method for identifying an enhancer of phagocytic clearance of free cholesterol-loaded macrophages, the method comprising
(a) labeling a free cholesterol-loaded macrophage; -
(b) culturing the free cholesterol-loaded macrophage in the presence of phagocytes and in the presence of a test compound, thereby providing a test sample; and (c) determining the amount of a label present in the phagocytes in the test sample, wherein, an increase in the amount of the label in the phagocytes in the presence of the test compound compared to the amount of the label present in the phagocytes cultured with free cholesterol-loaded macrophages in the absence of the test compound indicates that the compound is an enhancer of phagocytic clearance of a free cholesterol-loaded macrophages. - View Dependent Claims (4, 37, 41)
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- 16. A method for promoting clearance of apoptotic macrophages from advanced atherosclerotic lesions, the method comprising contacting an atherosclerotic lesion with a compound that promotes clearance of apoptotic macrophages.
- 19. A method for treating atherosclerosis or inhibiting the development of atherosclerosis in a subject, the method comprising administering to the subject a compound that enhances macrophage phagocytosis.
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20. A method for treating a subject at risk of having or having an atherosclerotic lesion, the method comprising administering to the subject a pharmaceutically effective amount of a compound that promotes clearance of apoptotic macrophages from advanced atherosclerotic lesions.
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21. A method for treating a subject at risk of having or having an atherosclerotic lesion, the method comprising administering to the subject a pharmaceutically effective amount of a compound that promotes clearance of necrotic macrophages from advanced atherosclerotic lesions.
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22. A method for treating a subject at risk of having or having an atherosclerotic lesion, the method comprising administering to the subject a pharmaceutically effective amount of a compound that promotes clearance of cholesterol-loaded macrophages from advanced atherosclerotic lesions.
- 34. A composition comprising an enhancer of phagocytic clearance of apoptotic macrophages (a phagocyte enhancer compound) and a pharmaceutically acceptable excipient.
Specification