Lipoproteins

1. Lipoproteins • Function: Transport of fat soluble substances • Types: 1) Chylomicron • 2) VLDL • 3) LDL • 4) HDL

2. Chylomicrons • Made by: the small intestines in the fed state • Absorbed into: the lymph vessels, then --> moves into the blood • Rich in: TGs • Function: Deliver TG’s to body cells to be used as fuel

3. Chylomicron Triglycerides 3 Fatty Acids Glycerol Adipose Skeletal Heart Blood (storage) Muscle (energy) (energy) Liver Chylomicron Remnant Liver

4. VLDL • = Very Low Density Lipoprotein • Made in: the liver from excess dietary carbohydrate and protein along with the Chylomicron remnant • Secreted into: the bloodstream • Rich in: TGs • Function: Deliver TGs to body cells • Contains apo B100 • Similar to Chylomicrons, but made by different tissues

5. VLDL Triglycerides 3 Fatty Acids Glycerol Adipose Skeletal Heart Blood (storage) Muscle (energy) (energy) Liver Once VLDL looses much of its TG’s it becomes LDL

6. LDL • = Low Density Lipoprotein • Made in: the Liver as VLDL • Arise from: VLDL once it has lost a lot of its TG’s • Secreted into: the bloodstream • Rich in: Cholesterol • Function: Deliver cholesterol to all body cells

7. HDL • = High Density Lipoprotein • Made in: the Liver and Small Intestine • Secreted into: the bloodstream • Function: Pick up cholesterol from body cells and take it back to the liver = “reverse cholesterol transport” • Potential to help reverse heart disease

9. Cardiovascular Disease (CVD) • Main type of CVD is Atherosclerosis (AS) • Endothelial dysfunction is one of earliest changes in AS • Mechanical, chemical, inflammatory mediators can trigger endothelial dysfunction: • High blood pressure • Smoking (free radicals that oxidatively damage endothelium) • Elevated homocysteine • Inflammatory stimuli • Hyperlipidemia

10. A Healthy Endothelium produces: áPGI2 áNO Maintaining an anti-coagulant, anti-thrombotic surface

11. A Dysfunctional Endothelium has decreased: âPGI2 âNO • Increased: • pro-inflammatory • molecules: • MCP-1 • TNFa • VCAM-1 Shifting to a pro-coagulant, pro-thrombotic surface

12. Pro-Inflammatory Molecules • Chemokines = monocyte chemoattractant protein 1 (MCP-1) • Inflammatory cytokines = tumor necrosis factor  (TNF) • Adhesion molecules = intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) • Overexpression of all these inflammatory mediators is commonly seen in atherosclerotic lesions.

13. Endothelial Dysfunction( endothelial activation, impaired endothelial-dependent vasodilation) • â endothelial synthesis of PGI2 (prostacylcin), & NO (nitric oxide) • PGI2 = vasodilator, âplatelet adhesion/aggregation • NO = vasodilator, âplatelet & WBC (monocyte) adhesion • á Adhesion of monocytes onto endothelium --> transmigration into subendothelial space (artery wall) --> change to macrophages • Endothelial dysfunction --> increased flux of LDL into artery wall

16. Oxidation of LDL (oxLDL) • Oxidation = process by which free radicals (oxidants) attack and damage target molecules / tissues • Targets of free radical attack: • DNA - carbohydrates • Proteins - PUFA’s>>> MUFA’s>>>>> SFA’s • LDL can be oxidatively damaged: PUFA’s are oxidized and trigger oxidation of apoB100 protein --> oxLDL • OxLDL is engulfed by macrophages in subendothelial space

19. Atherosclerotic Plaque • Continued endothelial dysfunction (inflammatory response) • Accumulation of oxLDL in macrophages (= foam cells) • Migration and accumulation of: • smooth muscle cells, • additional WBC’s (macrophages, T-lymphocytes) • Calcific deposits • Change in extracellular proteins, fibrous tissue formation • High risk = á VLDL (áTG) á LDL â HDL

20. Antioxidant Defense Systems • 1. Prevent oxidation from being initiated • 2. Halt oxidation once it has begun • 3. Repair oxidative damage

21. Antioxidant Mechanisms • Antioxidant vitamins (vitamins C, E, carotenoids) • Flavanoids and other phytochemicals • Antioxidant enzyme systems • Minerals required: Mn, Cu, Zn, Se

22. Factors Associated with CVD • Genetic Variables • Being male • Being post-menopausal female • Family history of heart disease before the age of 55 (some are associated with genetic defects in LDL receptors)

23. Factors Associated with CVD • Dietary 1. Elevated levels of LDL --More LDL around to potentially oxidize and accumulate in artery wall 2. Low levels of HDL --HDL carries cholesterol from artery walls back to the liver 3. Low levels of antioxidant vitamins --Vit. E, Vit. C, Beta-carotene 4. Low levels of other dietary antioxidants --Phenolics, flavanoids, red wine, grape juice, vegetables, fruits

24. Factors Associated with CVD • High blood pressure • Damages the artery wall allowing LDL to enter the wall more readily Cigarette Smoking • Cigarette smoke products are oxidants and can oxidize LDL • Cigarette smoking compromises the body’s antioxidant vitamin status, especially Vit. C • Damages the artery wall Activity Level • Exercise is the most effective means of raising HDL levels Obesity

25. Homocysteine Levels • Normal byproduct of certain metabolic pathways • Normally metabolized to other products • Elevated levels cause damage to artery walls = increased the oxidation of LDL • Elevated homocysteine levels are significantly correlated with increased risk to heart disease. • Vitamins B6, B12, and Folic acid normalize homocysteine levels.

26. Diet Methionine (a.a.) Enzymes B12, Folate Homocysteine SAM 1. Norepinephrine 2. Guanidinoacetate 3. Serotonin 4. Serine Enzyme B6 cysteine CH3 1. Epinephrine 2. Creatine 3. Melatonin 4. Choline SAH sulfate

27. Dietary/Lifestyle Prevention/Intervention of Heart Disease

28. Know Your Lipid Profile Fasting Blood Level Ideal, Healthy Level

29. Know Your Diabetes, Metabolic Risk Fasting Healthy Pre-Diabetes Diabetes (Metabolic Syndrome)

30. The Metabolic Syndrome

31. Know Your Blood Pressure Strive for blood pressure of 120/80 or less