The State Education Institution of Higher Professional Training

The State Education Institution of Higher Professional Training The First Sechenov Moscow State Medical University under Ministry of Health of the Russian Federation Department of Pathophysiology Disturbances of lipid metabolism. Atherosclerosis. Lecture presentation Professor Pirozhkov S. V. 2014 -2015 education year

TYPICAL DISORDERS OF LIPID METABOLISM ● Dislipidemia ► Hyperlipidemia ► Hypolipidemia ● Obesity ● Lipodystrophy ● Lipidosis

Types of hyperlipoproteinemia (Fredrickson, 1967) Type Plasma cholesterol levels I Hyperchylomicronemia IIa Hyper-β-lipoproteinemia IIb Hyper-β + pre-β-lipoproteinemia III Dys-β-lipoproteinemia IV Hyperpre-β-lipoproteinemia + hyperchylomicronemia Plasma TG levels N or N

MECHANISMS OF HYPERLIPOPROTEINEMIA 1. Abnormal structure of receptors for lipoproteins on the cell’s surface ■ familial hypercholesterolemia 2. Defective structure or lack of apoproteins ■ defective synthesis of apo-B 100, apo-E, apo. CII 3. Low activity of plasma lipoprotein lipase 4. Increased mobilization of lipids from the lipid stores

MANIFESTATIONS OF HYPERCHOLESTEROLEMIA Xanthomas and xanthelasmas Tendon xanthomas

MECHANISMS OF HYPOLIPOPROTEINEMIA 1. Lack of synthesis of apo-B protein ■ hypo-beta-lipoproteinemia 2. Defective formation of VLDL: ■ absence of the microsomal triglyceride transfer protein – a-beta-lipoproteinemia 3. Abnormal synthesis of apo-A protein ■ hypo-alfa-lipoproteinemia (Tangier disease)

BASIC FACTORS OF OBESITY Hormonal status Abnormal function of the leptin-αMSH-melanocortin 4 receptor system Disorders of hypothalamic appetite control CALORIES INTAKE OBESITY Psychological factors Cultural factors Daily physical activity Basal metabolic rate CALORIES EXPENDITURE

TYPES OF OBESITY ● Cortical ● Hypothalamic ● Endocrine ● Metabolic

Atherosclerosis is a chronic slowly progressive disease manifested by focal thickening of the intimal layer of elastic and muscular-elastic arteries due to deposition of lipids (lipoproteins) and reactive excrescence of connective tissue

Atherogenesis: Initiation stage LDL Modified LDL Chronic endothelial injury/dysfunction: ● Hemodynamic factors ● Hyperlipidemia ● Smoking ● Bacteria, viruses Increased expression of VCAM-1 Increased transmigration te cy o on m Endothelial cell Active free radicals TNFα, IL-1 Foam cell Scavenger receptor Chemotaxins

THE STRUCTURE OF ATHEROMA (FIBROUS PLAQUE) FIBROUS CAP (SMC, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans ) NECROTIC CENTER (cell debris, cholesterol, calcium) MEDIA

The main risk factors of atherosclerosis ► Hypercholesterolemia ► Arterial hypertension ► Smoking ► Diabetes mellitus ► Obesity ► Age, male sex ► Psychological stress, hypodynamia ► Genetics