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Pathogenesis of Acute Coronary Syndromes PowerPoint Presentation

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Description : Check out this medical presentation on Cerebrovascular Disease, which is titled "Pathogenesis of Acute Coronary Syndromes", to know about Pathogenesis of Acute Coronary Syndromes, Ischemic Heart Disease, Cerebrovascular Disease, and Peripheral Vascular Disease.

Tags : Cerebrovascular Disease, Pathogenesis, Acute Coronary Syndromes, Ischemic Heart Disease, Peripheral Vascular Disease

Published on : Jul 01, 2021 | Views : 1852 | Downloads : 3

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Slide 1-

Pathogenesis of Acute Coronary Syndromes Nathan Wong
Slide 2-

Schematic Time Course of Human Atherogenesis Transition from chronic to acute atheroma Ischemic Heart Disease Cerebrovascular Disease Peripheral Vascular Disease
Slide 3-

Normal Fatty Streak Fibrous Plaque Occlusive Atherosclerotic Plaque Plaque Rupture/ Fissure & Thrombosis MI Stroke Critical Leg Ischemia Clinically Silent Coronary Death Increasing Age Effort Angina Claudication Unstable Angina Atherosclerosis: A Progressive Process Courtesy of P Ganz.
Slide 4-

Libby P. Lancet. 1996;348:S4-S7. Media – T lymphocyte – Macrophage foam cell (tissue factor+) – “Activated” intimal SMC (HLA-DR+) – Normal medial SMC Fibrous cap Intima Lipid core Lumen The Anatomy of Atherosclerotic Plaque
Slide 5-

Nissen et al. In: Topol. Interventional Cardiology Update. 14;1995. Angiographically Inapparent Atheroma
Slide 6-

The Matrix Skeleton of Unstable Coronary Artery Plaque Davies MJ. Circulation. 1996;94:2013-2020. Fissures in the fibrous cap
Slide 7-

Libby P. Circulation. 1995;91:2844-2850. Characteristics of Plaques Prone to Rupture – T lymphocyte – Macrophage foam cell (tissue factor+) – “Activated” intimal SMC (HLA-DR+) – Normal medial SMC “Stable” plaque “Vulnerable” plaque Lumen area of detail Media Fibrous cap Lumen Lipid core Lipid core
Slide 8-

Libby P. Circulation. 1995;91:2844-2850. Proposed Mechanisms of Event Reduction by Lipid-Lowering Therapy Improved endothelium-dependent vasodilation Stabilization of atherosclerotic lesions especially nonobstructive, vulnerable plaques Reduction in inflammatory stimuli lipoproteins and modified lipoproteins Prevention, slowed progression, or regression of atherosclerotic lesions
Slide 9-

Atheroma are not merely filled with lipid, but contain cells whose functions critically influence atherogenesis: Intrinsic Vascular Wall Cells: Endothelium Smooth Muscle Cells Inflammatory Cells: Macrophages T Lymphocytes Mast Cells
Slide 10-

Cell Types in the Human Atheroma Monocyte/ Macrophage T-lymphocytes Tunica Media Intima Smooth muscle cells Endothelium
Slide 11-

No symptoms + Symptoms Schematic Time Course of Human Atherogenesis Time (y) Symptoms Lesion initiation Ischemic Heart Disease Cerebrovascular Disease Peripheral Vascular Disease
Slide 12-

Macrophage Functions in Atherogenesis Attachment
Slide 13-

Leukocyte–Endothelial Adhesion Molecules Mono T B PMN
Slide 14-

Vascular Cell Adhesion Molecule 1 (VCAM-1) Binds monocytes and lymphocytes - Cells found in atheroma Expressed by endothelium over nascent fatty streaks Expressed by microvessels of the mature atheroma
Slide 15-

An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium Li H et al. Arterioscler Thromb 1993;13:197-204.
Slide 16-

VCAM-1 Expression in Rabbit Aorta Li H et al. Arterioscler Thromb 1993;13:197-204. 3 weeks on atherogenic diet
Slide 17-

Penetration Macrophage Functions in Atherogenesis
Slide 18-

Monocyte Chemoattractant Protein 1 (MCP-1) A potent mononuclear cell chemoattractant Produced by endothelial and smooth muscle cells Localizes in human and experimental atheroma
Slide 19-

Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low-density lipoprotein receptor–deficient mice Gu L et al. Mol Cell 1998;2:275-281.
Slide 20-

Reduced Lipid Deposition in MCP-1–Deficient Atherosclerotic Mice Gu L et al. Mol Cell 1998;2:275-281. LDL-R –/– MCP-1 +/+ LDL-R –/– MCP-1 –/–
Slide 21-

Reduced Lipid Deposition in MCP-1–Deficient Atherosclerotic Mice Oil Red Staining % Aortic Surface Stained Time on Diet: 12 – 14 weeks +/+ -/- ** * +/+ -/- 20 – 25 weeks *P = 0.001 compared to +/+ **p = 0.005 compared to +/+
Slide 22-

Macrophage Functions in Atherogenesis Division
Slide 23-

Molecular Mediators of Atherogenesis M-CSF MCP-1 VCAM-1
Slide 24-

Matrix Metabolism and Integrity of the Plaque’s Fibrous Cap Libby P. Circulation 1995;91:2844-2850. + + + + + + – Synthesis Breakdown Lipid core IL-1 TNF- MCP-1 M-CSF Fibrous cap IFN- CD-40L Collagen-degrading Proteinases Tissue Factor Procoagulant
Slide 25-

Increased Expression of Interstitial Collagenase (CL) by Smooth Muscle Cells (SMC) and Macrophages (M) in Human Atheroma Galis ZS et al. J Clin Invest 1994;94:2493-2503.
Slide 26-

Plaque Rupture with Thrombosis Thrombus Fibrous cap 1 mm Lipid core Illustration courtesy of Frederick J. Schoen, M.D., Ph.D.
Slide 27-

Thrombosis of a Disrupted Atheroma, the Cause of Most Acute Coronary Syndromes, Results from: Weakening of the fibrous cap Thrombogenicity of the lipid core Illustration courtesy of Michael J. Davies, M.D.