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Inflammation and the Pathogenesis of Atherothrombotic DiseasePeter Libby, M.D. Atheroma are not merely filled with lipid, but contain cells whose functions critically influence atherogenesis: Cell Types in the Human Atheroma Schematic Time Course of Human Atherogenesis Macrophage Functions in Atherogenesis Leukocyte–Endothelial Adhesion Molecules Vascular Cell Adhesion Molecule 1(VCAM-1) An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium VCAM-1 Expression in Rabbit Aorta Macrophage Functions in Atherogenesis Monocyte Chemoattractant Protein 1(MCP-1) Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low-density lipoprotein receptor–deficient mice Reduced Lipid Deposition in MCP-1–Deficient Atherosclerotic Mice Reduced Lipid Deposition in MCP-1–Deficient Atherosclerotic Mice Macrophage Functions in Atherogenesis Macrophage Functions in Atherogenesis Macrophage Colony-Stimulating Factor (M-CSF) Augmented M-CSF gene expression in human and experimental atherogenesis M-CSF Expression in Atheroma M-CSF Promotes Atherogenesis M-CSF Deficiency (op mutation) Reduces Atheroma in LDL Receptor–Knockout Mice M-CSF Gene Dosage Relates to Atheroma Size in LDLR –/– Mice Molecular Mediators of Atherogenesis Anatomy of the Atherosclerotic Plaque Schematic Time Course of Human Atherogenesis Thrombosis of a Disrupted Atheroma, the Cause of Most Acute Coronary Syndromes, Results from: Matrix Metabolism and Integrity of the Plaque’s Fibrous Cap Increased Expression of Interstitial Collagenase (CL) by Smooth Muscle Cells (SMC) and Macrophages (M?) in Human Atheroma Plaque Rupture with Thrombosis Thrombosis of a Disrupted Atheroma, the Cause of Most Acute Coronary Syndromes, Results from: CD40 and Tissue Factor in Atheroma CD40 Ligation Induces Tissue Factor Expression in Human Monocyte-Derived Macrophages Log Fluorescence Cell Numbers 160 120 80 40 0 160 120 80 40 0 100 101 1