1. 03/06/231 K 305 23 June 03

2. 03/06/232 Atherosclerosis Etiology Classic Risk Factors Dyslipidemia Low HDL Epidemiological Studies (e.g. Framingham) Genetic Disorders Tangier Disease

3. 03/06/233 Atherosclerosis Etiology Classic Risk Factors Hypertension Obesity Diabetes (uncontrolled) Inactivity Smoking Gender

4. 03/06/234 Atherosclerosis Emerging Risk Factors Homocysteine (folic acid) C Reactive Protein Lipoprotein a platelet reactivity small dense LDL particle size elevated Fe

5. 03/06/235 Etiology of Atherosclerosis

6. 03/06/236 Excess LDL cholesterol accumulates in arterial wall Oxidation of LDL phospholipids containing arachidonic Ox-LDL stimulate endothelial cell to display sVCAM-1 monocytes and T cells to adhere to the intimal wall penetrate intima due to the effect of macrophage chemoattractant protein-1 (MCP-1) Inside the initma the monocytes differentiate into macrophages oxidized LDL hypothesis

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8. 8 LDL oxidized by OFR and taken up into macrophages via scavenger receptor - become foam cells and fatty streak Ox-LDL can inhibit normal endothelial functions causing reduced NOS activity and a procoagulant surface cytokines and growth factors released by cells within region cause VSM proliferation and migration tough fibrous cap is produced by cells within plaque. Inflammatory substances secreted by foam cells may cause plaque to weaken by proteolysis of matrix proteins foam cells may display a factor which promotes blood clotting possibly causing a thrombus oxidized LDL hypothesis (con’t)

9. 03/06/239 response-to-injury hypothesis Various damaging agents chronically present alter endothelial function Increased presence of soluble vascular cell adhesion molecule-1 (sVCAM-1) Platelet and leukocyte aggregation which is normally kept in check by healthy endothelial cells occur Release of growth factors from platelets (e.g. platelet derived growth factor - PDGF) which can stimulate VSM proliferation and change in phenotype

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14. 03/06/2314 Treatment of Atherosclerosis

15. 03/06/2315 Diet  intake of saturated and hydrogenated fats  total calories from fats  cholesterol intake  total caloric intake  intake of soluble fibre  intake of omega-3 FA Exercise decreases morbidity and mortality from CAD stress management quit smoking manage diabetes Lifestyle changes

16. 03/06/2316  LDL [cholesterol] by statins HMG CoA reductase inhibitors Statin therapy reduces coronary artery disease morbidity and mortality in primary and secondary prevention trials  [cholesterol] uptake by GI tract take folic acid to reduce [homocysteine] aspirin to reduce chance of clotting  MAP manage blood glucose if diabetic Pharmacological

17. 03/06/2317 CABG Angioplasty restenosis through intimal hyperplasia is a serious problem – may use stents use gene therapy to reduce this side effect Genes that disrupt cell cycle transcription factors and intracellular signals inducible form of iNOS - NO which is a potent vasodilator also inhibits platelet and leukocyte adhesion, VSM proliferation and migration Surgical procedures