Causes High blood cholesterol High blood pressure Smoking
동맥경화증의 원인 Causes • • • High blood cholesterol High blood pressure Smoking Obesity Lack of physical activity
동맥경화증의 위험인자 Risk Factors Uncontrollable Controllable • Sex • High blood pressure • Hereditary • High blood cholesterol • Race • Smoking • Age • Physical activity • Obesity • Diabetes • Stress and anger
Cholesterol Crystals/Foam Cells
Endothelial Dysfunction • Increased endothelial permeability to lipoproteins and plasma • Up-regulation of leukocyte adhesion molecules • Migration of leukocytes into artery wall Ross, NEJM; 1999
Formation of Fatty Streak • T-Cell activation • Foam-cell formation • Platelet adherence and aggregation stimulated by integrins, P-selectin, fibrin, TXA 2, and TF. Ross, NEJM; 1999
Formation of Advanced, Complicated Lesion • Fibrous cap forms in response to injury to wall off lesion from lumen. • Fibrous cap covers a mixture of leukocytes, lipid and debris which may form a necrotic core. • Necrotic core results from apoptosis and necrosis, increased proteolytic activity and lipid accumulation. Ross, NEJM; 1999
Development of Unstable Fibrous Plaque • Rupture or ulceration of fibrous cap rapidly leads to thrombosis. • Occurs primarily at sites of thinning of the fibrous cap. • Thinning is a result of continuing influx of and activation of macrophages which release metalloproteinases and other proteolytic enzymes. • These enzymes degrade the matrix which can lead to hemorrhage and thrombus formation Ross, NEJM; 1999
Role of LDL in Atherosclerosis LDL Readily Enter the Artery Wall Where They May be Modified Vessel Lumen LDL Endothelium Oxidation of Lipids and Apo. B LDL Aggregation Hydrolysis of Phosphatidylcholine to Lysophosphatidylcholine Other Chemical Modifications Modified LDL are Proinflammatory Steinberg D et al. N Engl J Med 1989; 320: 915 -924. Intima
Role of LDL in Atherosclerosis Vessel Lumen Monocyte LDL MCP-1 Endothelium LDL Modified LDL Intima Navab M et al. J Clin Invest 1991; 88: 2039 -2046.
Role of LDL in Atherosclerosis Vessel Lumen Monocyte LDL MCP-1 Endothelium LDL Intima Modified LDL Macrophage Steinberg D et al. N Engl J Med 1989; 320: 915 -924. Modified LDL Promote Differentiation of Monocytes into Macrophages
Role of LDL in Atherosclerosis Vessel Lumen Monocyte LDL Adhesion Molecules MCP-1 Cytokines Endothelium LDL Modified LDL Macrophage Nathan CF. J Clin Invest 1987; 79: 319 -326. Intima
Role of LDL in Atherosclerosis Vessel Lumen Monocyte LDL Adhesion Molecules MCP-1 Endothelium LDL Modified LDL Taken up by Macrophage Foam Cell Macrophage Steinberg D et al. N Engl J Med 1989; 320: 915 -924. Intima
Role of LDL in Atherosclerosis Vessel Lumen Monocyte Remnant Lipoproteins Adhesion Molecules Endothelium MCP-1 Cytokines Macrophage Doi H et al. Circulation 2000; 102: 670 -676. Remnants Modified Remnants Foam Cell Intima Growth Factors Metalloproteinases Cell Proliferation Matrix Degradation
HDL Prevent Foam Cell Formation Vessel Lumen Monocyte LDL Adhesion Molecules MCP-1 Endothelium LDL Modified LDL Cytokines Macrophage Foam Cell HDL Promote Cholesterol Efflux Miyazaki A et al. Biochim Biophys Acta 1992; 1126: 73 -80. Intima
HDL Inhibits Oxidative Modification of LDL Vessel Lumen Monocyte LDL Adhesion Molecules MCP-1 Endothelium LDL Modified LDL Cytokines Macrophage Foam Cell HDL Promote Cholesterol Efflux Mackness MI et al. Biochem J 1993; 294: 829 -834. HDL Inhibit Oxidation of LDL Intima
HDL Inhibits Expression of Adhesion Molecules Monocyte HDL Inhibit Adhesion Molecule Expression LDL Adhesion Molecules MCP-1 Endothelium LDL Modified LDL Cytokines Macrophage HDL Inhibit Oxidation of LDL Foam Cell HDL Promote Cholesterol Efflux Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995; 15: 1987 -1994. Vessel Lumen Intima
Response to Injury Endothelial Dysfunction
Initiation of Fatty Streak
Fibro-fatty Atheroma
Coronary Artery Atherosclerosis
ATHEROSCLEROSIS: Pathology, Pathogenesis, Complications, Natural History
고혈압증 hypertension 혈압유지 기전에 이상이 있어 지속적으로 혈압이 높은 병적 상태 Normal Blood Pressure of < 140/ 90 Blood Pressure of 130 to 139/ 85 to 89 should be closely watched High Blood Pressure > 140/ 90 Top number (Systolic 수축기)= Pressure while heart is beats Bottom number (Diastolic 이완기)= Pressure while heart is resting between beats
Classification and management of BP for adults
What Causes High Blood Pressure? Controllable Risk Factors Increased salt intake Obesity Alcohol Stress Lack of exercise Uncontrollable Risk Factors Heredity Age Men between age 35 and 50 Women after menopause Race 1/3 African Americans Higher incidence in non-Hispanic blacks and Mexican Americans
What does High Blood Pressure do to my Body? Stroke Congestive heart failure Kidney failure Heart attack Heart rhythm problems Aneurysm
What Can I Do? - High blood pressure is a lifelong disease - Blood pressure can be controlled not cured - Controlling blood pressure will reduce the risk of stroke, heart attack, heart failure and kidney disease - Loose weight if your overweight - Get regular physical activity - Avoid excessive alcohol - Stop smoking - Manage your stress - Decrease salt intake - Eat for heart health - Discuss the use of oral contraceptives with your doctor - Discuss the use of some medications with your doctor
본태성 고혈압증 Primary (essential) hypertension) 혈압증의 90% Chronic elevation in blood pressure that occurs without evidence of other disease 원인 : 유전, 짠 음식, 비만증, 스트레스, 흡연
이차성 (연발성) 고혈압증 Secondary hypertension) Elevation of blood pressure that results from some other disorder, such as kidney disease
- Slides: 42