순환기질환 - 혈관, 림프관 -

동맥경화증 arteriosclerosis 나이가 들면서 혈관의 기능이 약화되어 동맥벽의 경화, 비후가 나타나는 만성적 병변을 총칭 죽상동맥경화증 / 세동맥경화증 / 동맥류 aneurysm Aortic Aneurysm

동맥경화증에 의한 순환장애

동맥경화증의 원인 Causes High blood cholesterol High blood pressure Smoking Obesity Lack of physical activity

동맥경화증의 위험인자 Risk Factors Uncontrollable Controllable Sex Hereditary Race Age High blood pressure High blood cholesterol Smoking Physical activity Obesity Diabetes Stress and anger

동맥경화증의 치료 Treatement

죽상동맥경화증 atherosclerosis 탄력성 동맥(대동맥, 폐동맥줄기)이나 근형동맥(심장동맥, 신동맥, 뇌저부동맥, 장간막동맥 등의 장기동맥)에 발생하는 동맥경화 유형  죽상경화 반점(atheroma)이 내강에 형성  콜레스테린결정

Cholesterol Crystals/Foam Cells

죽상동맥경화증의 발생기전

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, TXA2, 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 Steinberg D et al. N Engl J Med 1989;320:915-924. Endothelium Vessel Lumen LDL LDL Readily Enter the Artery Wall Where They May be Modified Intima Modified LDL Modified LDL are Proinflammatory Hydrolysis of Phosphatidylcholine to Lysophosphatidylcholine Other Chemical Modifications Oxidation of Lipids and ApoB Aggregation Role of LDL in inflammation LDL readily enters the artery wall by crossing the endothelial membrane. Once in the arterial wall, if LDL accumulates, it is subject to a variety of modifications. The best known of these is oxidation, both of the lipids and of the apo B. LDL is also subject to aggregation, and its phospholipids are subject to hydrolysis by phospholipases to form lysophosphatidylcholine. Several other chemical modifications have also been reported. The net effect of these changes is the production of a variety of modified LDL particles, and the evidence is now very strong that these modified LDL particles are proinflammatory. Reference: Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989;320:915-924.

Role of LDL in Atherosclerosis Navab M et al. J Clin Invest 1991;88:2039-2046. Endothelium Vessel Lumen Intima Monocyte Modified LDL MCP-1 Modified LDL stimulate expression of MCP-1 in endothelial cells Modified LDL is involved in many stages of the inflammatory process that leads to the development of atherosclerosis. Modified LDL activates endothelial cells to express monocyte chemotactic protein 1 (MCP-1), which attracts monocytes from the vessel lumen and into the subendothelial space, in what is one of the very early stages in the inflammatory process leading to the development of atherosclerosis.

Role of LDL in Atherosclerosis Steinberg D et al. N Engl J Med 1989;320:915-924. Endothelium Vessel Lumen Intima Monocyte Modified LDL Modified LDL Promote Differentiation of Monocytes into Macrophages MCP-1 Macrophage Differentiation of monocytes into macrophages The modified LDL plays an important role in promoting the differentiation of monocytes into macrophages, a key step in the inflammatory process on the way to the development of atherosclerosis. Reference: Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989;320:915-924.

Role of LDL in Atherosclerosis Nathan CF. J Clin Invest 1987;79:319-326. Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 Adhesion Molecules Cytokines Intima Modified LDL induces macrophages to release cytokines that stimulate adhesion molecule expression in endothelial cells After modified LDL promotes the differentiation of monocytes into macrophages, the macrophages release a variety of chemicals, including cytokines. Of these cytokines, tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) activate endothelial cells to express adhesion molecules that bind monocytes, making them available for recruitment into the subendothelial space by MCP-1. Reference: Nathan CF. Secretory products of macrophages. J Clin Invest 1987;79:319-326.

Role of LDL in Atherosclerosis Endothelium Vessel Lumen Monocyte Macrophage MCP-1 Adhesion Molecules Steinberg D et al. N Engl J Med 1989;320:915-924. Foam Cell Modified LDL Taken up by Macrophage Intima Macrophages express receptors that take up modified LDL The activated macrophages also express a variety of scavenger receptors, several of which recognize the different forms of modified LDL. The macrophages take up the LDL through these scavenger receptors, accumulate the lipid, and are converted into the lipid-rich foam cells that are the hallmark of atherosclerosis. Reference: Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989;320:915-924.

Role of LDL in Atherosclerosis Endothelium Vessel Lumen Monocyte Macrophage MCP-1 Adhesion Molecules Foam Cell Intima Modified Remnants Cytokines Cell Proliferation Matrix Degradation Doi H et al. Circulation 2000;102:670-676. Growth Factors Metalloproteinases Remnant Lipoproteins Remnants The remnants of VLDL and chylomicrons are also pro-inflammatory VLDL remnants and chylomicron remnants behave in much the same way as LDL. They enter the subendothelial space, where they become modified, and the modified remnants stimulate MCP-1, promote the differentiation of monocytes into macrophages, and are taken up by the macrophages to form foam cells. Like LDL, the remnant lipoproteins are proinflammatory and proatherogenic. References: Doi H, Kugiyama K, Oka H, Sugiyama S, Ogata N, Koide SI, Nakamura SI, Yasue H. Remnant lipoproteins induce proatherothrombogenic molecules in endothelial cells through a redox-sensitive mechanism. Circulation 2000;102:670-676.

HDL Prevent Foam Cell Formation LDL Miyazaki A et al. Biochim Biophys Acta 1992;1126:73-80. Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 Adhesion Molecules Cytokines Intima HDL Promote Cholesterol Efflux Foam Cell HDL prevent formation of foam cells Perhaps the best-known function of HDL is the promotion of cholesterol efflux from cells. Efflux of cholesterol from foam cells leads to a reduction in foam cell formation; although the macrophages may accumulate, they are not converted into foam cells. As a result, the inflammatory process is arrested to a certain extent. Therefore, HDL is anti-inflammatory and also protects against the development of atherosclerosis.

HDL Inhibits Oxidative Modification of LDL Mackness MI et al. Biochem J 1993;294:829-834. Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 Adhesion Molecules Cytokines Foam Cell HDL Promote Cholesterol Efflux Intima HDL Inhibit Oxidation of LDL HDL inhibit the oxidative modification of LDL HDL has protective effects in addition to promoting cholesterol efflux. One of the best known of these is the ability to inhibit the oxidation of LDL. To the extent that LDL oxidation is an important step in the development of the inflammatory process, this property of HDL is clearly anti-inflammatory.

HDL Inhibits Expression of Adhesion Molecules LDL Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994. Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 Adhesion Molecules Cytokines Intima HDL Inhibit Oxidation of LDL HDL Inhibit Adhesion Molecule Expression Foam Cell HDL Promote Cholesterol Efflux Inhibition of adhesion molecules The cytokine-induced expression of adhesion molecules in endothelial cells has been shown in vitro and more recently in vivo to be inhibited by HDL, in a process that potentially blocks a very early inflammatory stage in the development of atherosclerosis.

세동맥경화증 artheriosclerosis 세동맥에 생기는 동맥경화증 유리질 세동맥경화증(hyaline arteriosclerosis) : 만성 고혈압 동반, 동맥벽의 유리화 증식 세동맥경화증(hyperplasstic arteriosclerosis) : 급성의 심한 고혈압, 평활근 중심의 과형성 발생  섬유소성 괴사

세동맥경화증의 발생기전 Normal Artery

Endothelial Dysfunction Response to Injury Endothelial Dysfunction

Initiation of Fatty Streak

Fibro-fatty Atheroma

Coronary Artery Atherosclerosis

Pathology, Pathogenesis, Complications, Natural History ATHEROSCLEROSIS: Pathology, Pathogenesis, Complications, Natural History

고혈압증 hypertension Normal Blood Pressure Blood Pressure of < 140/ 90 혈압유지 기전에 이상이 있어 지속적으로 혈압이 높은 병적 상태 Normal Blood Pressure Blood Pressure of < 140/ 90 Blood Pressure of 130 to 139/ 85 to 89 should be closely watched High Blood Pressure 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? 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 Controllable Risk Factors Increased salt intake Obesity Alcohol Stress Lack of exercise

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