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Pathogenesis of Acute Coronary Syndromes PowerPoint Presentation

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Description : Check out this medical presentation on Atherosclerosis, which is titled "Pathogenesis of Acute Coronary Syndromes", to know about acute coronary syndrome, a term used to describe a range of conditions associated with sudden, reduced blood flow to the heart.

Tags : Atherosclerosis, Pathogenesis, Acute Coronary Syndromes, blood flow, heart, Atherogenesis, chronic, acute atheroma, Ischemic Heart Disease, Cerebrovascular Disease, Peripheral Vascular Disease

Published on : Jun 02, 2021 | Views : 2304 | Downloads : 5

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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.