Lipoproteins Function: Transport of fat soluble substances

Types:1) Chylomicron

2) VLDL

3) LDL

4) HDL

ChylomicronsMade by: the small intestines in the fed stateAbsorbed into: the lymph vessels, then --> moves into the bloodRich in: TGsFunction: Deliver TGs to body cells to be used as fuel

ChylomicronTriglycerides

3 Fatty AcidsGlycerol

AdiposeSkeletalHeart Blood(storage)Muscle(energy)(energy) Liver

Chylomicron Remnant

Liver

VLDL= Very Low Density LipoproteinMade in: the liver from excess dietary carbohydrate and protein along with the Chylomicron remnantSecreted into: the bloodstreamRich in: TGsFunction: Deliver TGs to body cellsContains apo B100Similar to Chylomicrons, but made by different tissues

VLDLTriglycerides

3 Fatty Acids Glycerol

AdiposeSkeletalHeart Blood(storage)Muscle(energy)(energy) Liver

Once VLDL looses much of its TGs it becomes LDL

LDL= Low Density LipoproteinMade in: the Liver as VLDLArise from: VLDL once it has lost a lot of its TGsSecreted into: the bloodstreamRich in: CholesterolFunction: Deliver cholesterol to all body cells

HDL= High Density LipoproteinMade in: the Liver and Small IntestineSecreted into: the bloodstreamFunction: Pick up cholesterol from body cells and take it back to the liver = reverse cholesterol transportPotential to help reverse heart disease

Cardiovascular Disease (CVD)Main type of CVD is Atherosclerosis (AS)Endothelial dysfunction is one of earliest changes in ASMechanical, chemical, inflammatory mediators can trigger endothelial dysfunction:High blood pressure Smoking (free radicals that oxidatively damage endothelium)Elevated homocysteineInflammatory stimuliHyperlipidemia

A Healthy Endotheliumproduces: PGI2 NOMaintaining ananti-coagulant, anti-thrombotic surface

A Dysfunctional Endotheliumhas decreased: PGI2 NOShifting to apro-coagulant, pro-thrombotic surfaceIncreased:pro-inflammatorymolecules:MCP-1TNFaVCAM-1

Pro-Inflammatory MoleculesChemokines = 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.

Endothelial Dysfunction( endothelial activation, impaired endothelial-dependent vasodilation) endothelial synthesis of PGI2 (prostacylcin), & NO (nitric oxide)PGI2 = vasodilator, platelet adhesion/aggregationNO = vasodilator, platelet & WBC (monocyte) adhesion

Adhesion of monocytes onto endothelium --> transmigration into subendothelial space (artery wall) --> change to macrophages

Endothelial dysfunction --> increased flux of LDL into artery wall

Oxidation of LDL (oxLDL)Oxidation = process by which free radicals (oxidants) attack and damage target molecules / tissuesTargets of free radical attack: DNA - carbohydrates Proteins - PUFAs>>> MUFAs>>>>> SFAs

LDL can be oxidatively damaged: PUFAs are oxidized and trigger oxidation of apoB100 protein --> oxLDL

OxLDL is engulfed by macrophages in subendothelial space

Atherosclerotic Plaque

Continued endothelial dysfunction (inflammatory response)Accumulation of oxLDL in macrophages (= foam cells) Migration and accumulation of: smooth muscle cells, additional WBCs (macrophages, T-lymphocytes)Calcific depositsChange in extracellular proteins, fibrous tissue formation

High risk = VLDL (TG) LDL HDL

Antioxidant Defense Systems1. Prevent oxidation from being initiated 2. Halt oxidation once it has begun

3. Repair oxidative damage

Antioxidant MechanismsAntioxidant vitamins (vitamins C, E, carotenoids)

Flavanoids and other phytochemicals

Antioxidant enzyme systems Minerals required: Mn, Cu, Zn, Se

Factors Associated with CVDGenetic VariablesBeing maleBeing post-menopausal femaleFamily history of heart disease before the age of 55 (some are associated with genetic defects in LDL receptors)

Factors Associated with CVD Dietary1. Elevated levels of LDL --More LDL around to potentially oxidize and accumulate in artery wall2. Low levels of HDL--HDL carries cholesterol from artery walls back to the liver3. Low levels of antioxidant vitamins--Vit. E, Vit. C, Beta-carotene4. Low levels of other dietary antioxidants--Phenolics, flavanoids, red wine, grape juice, vegetables, fruits

Factors Associated with CVDHigh blood pressure Damages the artery wall allowing LDL to enter the wall more readily Cigarette SmokingCigarette smoke products are oxidants and can oxidize LDLCigarette smoking compromises the bodys antioxidant vitamin status, especially Vit. CDamages the artery wall Activity LevelExercise is the most effective means of raising HDL levels Obesity

Homocysteine LevelsNormal byproduct of certain metabolic pathwaysNormally metabolized to other productsElevated levels cause damage to artery walls = increased the oxidation of LDLElevated homocysteine levels are significantly correlated with increased risk to heart disease.Vitamins B6, B12, and Folic acid normalize homocysteine levels.

Methionine (a.a.)SAMSAHHomocysteineCH3cysteinesulfate1. Norepinephrine2. Guanidinoacetate3. Serotonin4. Serine1. Epinephrine2. Creatine3. Melatonin4. CholineDietEnzymes B12, FolateEnzyme B6

Dietary/Lifestyle Prevention/Intervention of Heart Disease

Maintain Endothelial FunctionPlateletActivityDecrease LDLIncrease HDLIncrease Antioxidants High Blood Pressure w-3 PUFAs w -6 PUFA Saturated Fat MUFA/ PUFA MUFA/ w -6 PUFA HomocysteineB6, B12, Folic Acid Phytochemicals Cholesterol w-3 PUFAs (fish)Vegetables PhytochemicalsAspirin w-3 oils (fish) Exercise FruitsStop smoking Fiber Stop smokingStop smoking Trans FatsBody weight if overweight Fiber

Know Your Lipid ProfileFasting Blood Level Ideal, Healthy Level

Total Cholesterol< 200 mg/dlLDL-Cholesterol< 100 mg/dlHDL-Cholesterol 60 mg/dlTriglycerides< 150 mg/dl

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

Blood Glucose< 110 mg/dl110-125 mg/dl 126 mg/dl2 hr GTT< 140 mg/dl140-200 mg/dl> 200 mg/dlTriglyceride< 150 mg/dl> 150 mg/dlTypically elevatedHDL 60 mg/dlM < 40 mg/dlF < 50 mg/dlTypically low

The Metabolic Syndrome

Abdominal Obesity Men Women> 40 inch waist> 35 inch waistTriglycerides 150 mg/dLHDL cholesterol Men Women< 40 mg/dL< 50 mg/dLBlood Pressure 130/ 85 mm HgFasting Blood Glucose110-125 mg/dL

Know Your Blood PressureStrive for blood pressure of 120/80 or less

CategorySystolic (mm/Hg)Diastolic (mm/Hg)Normal120 or less80 or lessHigh Normal130-13985-89High Blood Pressure140 or more90 or more