Student%20Lecture%2021%20%28Hypercholesterolemia%29

Student%20Lecture%2021%20%28Hypercholesterolemia%29 -...

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Unformatted text preview: Lecture 21 Hypercholesterolemia Hypercholesterolemia Thursday 4­1­10 Announcements Outline Outline – Proof of completion of online course evaluation. Due 5­7­10. – Proof of attending a Purdue Sporting event (ticket stub and picture) plus ½ page summary of applying concept learned in HK368 to what you observed. Due 5­7­10. – Ultrasound practice subject. Contact: [email protected] Monday and Friday – 8:30am to 12:30pm Tuesday and Thursday – 9:30am Wednesday – 8:30am to 11:30am Lecture – Seminar – April 14th, 3:30pm, Armstrong 1109 – Hypercholesterolemia Cholesterol Cholesterol Steroidal alcohol (lipid) Consists of 4 joined rings, 2 methyl groups, and 8 carbon side chains Essential component – – – Unlike other lipids in that is not used in Lauralee Sherwood Sources Sources – Animal products contain cholesterol. – Plant products do not contain cholesterol. – Cholesterol can be manufactured in the liver. Cholesterol Transport Cholesterol in blood Cholesterol in blood Lipoproteins transport cholesterol in the blood. Lipoproteins comprised of – Soluble phospholipids Apoproteins – – Activate lipolytic enzymes – Reactive site that cells can recognize for endocytosis Insoluble cholesterol esters Triglycerides Carol Mattson Porth Types of Cholesterol Transporters Types Classified by their densities as assessed by ultracentrifugation Carol Mattson Porth Chylomicrons Chylomicrons of lipoproteins Synthesized in wall of Transport dietary cholesterol and triglycerides to Remnant chylomicron fragments and cholesterol transported to liver. Carol Mattson Porth VLDL VLDL Synthesized in the Transport triglycerides from At tissue triglycerides are removed and cholesterol remains Carol Mattson Porth IDL IDL IDL fragments are reduced in triglycerides and rich in cholesterol. Carol Mattson Porth LDL “Bad Cholesterol” LDL of LDL is removed from blood via receptor mediated pathways. of these receptors located on liver. Majority of LDL metabolism occurs in liver. of LDL is removed from blood via non receptor mediated pathways. – – Carol Mattson Porth HDL “Good Cholesterol” HDL Carries cholesterol from In liver the cholesterol can be used for the production of bile acid and excreted Carol Mattson Porth What are the health implications of elevated cholesterol? of McArdle, Katch and Katch McArdle, Katch and Katch Carol Mattson Porth Cholesterol Statistics Cholesterol Average cholesterol of Americans million Americans > 200mg/dl million Americans > 240mg/dl million doctors visits for cholesterol check yearly – mg/dl Total Cholesterol Statistic by Race and Gender and Men White African­Americans Mexican­Americans >200mg/dl 44.1% >240mg/dl 16.1% 16.0% Women White African­Americans Mexican­Americans >200mg/dl 42.1% >240mg/dl 18.2% 14.2% LDL Cholesterol Statistic by Race and Gender and Men White African­Americans Mexican­Americans >130mg/dl 31.7% 32.4% Women White African­Americans Mexican­Americans >130mg/dl 33.8% 30.7% HDL Cholesterol Statistic by Race and Gender and Men White African­Americans Mexican­Americans <40mg/dl 26.2% 27.7% Women White African­Americans Mexican­Americans <40mg/dl 6.9% 13.0% Causes of Hypercholesterolemia Causes Genetic – Gene mutation for receptor (most LDL cholesterol is removed by receptor dependent mechanisms). Rates of occurrence Heterozygotes Homozygotes – – – – Plasma LDL – Myocardial infarction before Plasma LDL 1 Myocardial infarction Xanthomas (LDL deposits in skin and tendons) (LDL Causes of Hypercholesterolemia Causes Lifestyle – – – – Increase VLDL an subsequently LDL Down regulate LDL receptors thus decreasing the LDL removal from blood Increase cholesterol synthesis and suppress LDL receptor activity Decreases HDL Pharmacological Interventions Pharmacological – Inhibits HMG­CoA reductase a key enzyme in production of cholesterol in the liver – Statins – Prevent reabsorption of bile acid in the intestine by chylomicrons – Cholestyramine – Prevents the absorption of dietary cholesterol in intestine – Ezetimibe – Blocks synthesis and release of VLDL by liver – Blocks synthesis of VLDL from chylomicron fragments Nutritional interventions Nutritional – Excessive calorie consumption lowers HDL – Each 1% of saturated fat relative to caloric intake increases cholesterol levels by 2.8mg/dl – 100 mg of ingested cholesterol increases cholesterol levels by 8­10mg/dl Exercise Total cholesterol Total cholesterol LDL HDL – – – These findings are troubling to exercise physiologists exercise Rapacz Swine Rapacz LDL receptor mutation (similar to familial hypercholesterolemia) – Methods Methods Endurance exercise trained (n=13) – trained on a treadmill (5 exercise bouts/week at an intensity of 75% of maximal exercise capacity and a duration of 40 to 80 minutes) for 16 weeks. Sedentary controls (n=12) Atherosclerosis severity (disease) Swine Characteristics Swine Sedentary (n=12) Exercise (n=13) Weight (kg) Heart/Body weight Time to exhaustion - Before Time to exhaustion - After Time Total cholesterol – Before Total (mg/dL) (mg/dL) Total Cholesterol – After (mg/dL) HDL – Before (mg/dL) HDL – After (mg/dL) Non-HDL – Before (mg/dL) Non-HDL – After (mg/dL) 76.7 ± 2.7 76.7 2.7 3.3 ± 0.1 3.3 0.1 18.8 ± 1.2 18.8 1.2 19.1 ± 0.8 19.1 0.8 362.5 ± 11.9 362.5 11.9 291.9 ± 17.1 291.9 17.1 28.8 ± 1.1 28.8 1.1 39.9 ± 1.8 39.9 1.8 333.7 ± 12.3 333.7 12.3 251.9 ± 16.6 251.9 16.6 71.5 ± 2.1 71.5 2.1 4.1 ± 0.06 4.1 0.06 22.9 ± 1 22.9 31.3 ± 0.8 31.3 0.8 345 ± 21.9 345 21.9 337.9 ±17.7 337.9 28.7 ± 1.2 28.7 1.2 33.7 ± 1.5 33.7 1.5 316.3 ± 22.2 316.3 22.2 304.1 ± 17.6 304.1 17.6 p 0.14 <0.001 0.01 0.01 <0.001 0.43 0.07 0.95 0.01 0.39 0.04 100 80 INTACT A + + + + + 100 80 B INDOMETHACIN + 100 80 E INTACT % Relaxation % Relaxation 60 40 20 0 -20 -11 -10 -9 * * * BRACHIAL - EX BRACHIAL - SED FEMORAL - EX FEMORAL - SED % Relaxation 60 40 20 0 + * 60 40 20 0 -20 -11 -10 -9 -8 -7 -6 BRACHIAL - EX BRACHIAL - SED FEMORAL - EX FEMORAL - SED * * -9 -8 -7 -6 * -8 -7 BRACHIAL - EX BRACHIAL - SED FEMORAL - EX FEMORAL - SED -6 -5 -4 -3 -20 -11 -10 -5 -4 -3 -5 -4 -3 Acetylcholine [Log M] Acetylcholine [Log M] Sodium Nitroprusside [Log M] 100 80 L-NAME 100 80 L-NAME + INDOMETHACIN % Relaxation 60 40 + + + % Relaxation C * -9 -8 ++++++ D + + 60 40 20 0 20 0 -20 -11 -10 BRACHIAL - EX BRACHIAL - SED FEMORAL - EX FEMORAL - SED * * -9 -8 -7 -6 BRACHIAL - EX BRACHIAL - SED FEMORAL - EX FEMORAL - SED -7 -6 -5 -4 -3 -20 -11 -10 -5 -4 -3 Acetylcholine [Log M] Acetylcholine [Log M] 50 40 % Staining 30 20 10 0 Femoral Brachial Carotid Th. Aorta LAD Sedentary Exercise Take Home Message Take ...
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This note was uploaded on 02/17/2011 for the course HK 458 taught by Professor Newcomer during the Spring '10 term at Purdue.

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