Lipoproteins• Function: Transport of fat soluble substances

• Types: 1) Chylomicron

2) VLDL

3) LDL

4) HDL

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

ChylomicronTriglycerides

3 Fatty Acids Glycerol

Adipose Skeletal Heart Blood(storage) Muscle (energy)

(energy) Liver

Chylomicron Remnant

Liver

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

VLDLTriglycerides

3 Fatty Acids Glycerol

Adipose Skeletal Heart Blood(storage) Muscle (energy)

(energy) Liver

Once VLDL looses much of its TG’s it becomes LDL

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

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

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

A Healthy Endotheliumproduces: PGI2

NO

Maintaining ananti-coagulant, anti-thrombotic surface

A Dysfunctional Endotheliumhas decreased: PGI2

NO

Shifting to apro-coagulant, pro-thrombotic surface

Increased:pro-inflammatory

molecules:MCP-1TNF

VCAM-1

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.

Endothelial Dysfunction( endothelial activation, impaired endothelial-dependent

vasodilation)

• endothelial synthesis of PGI2 (prostacylcin), & NO (nitric oxide)– PGI2 = vasodilator, platelet adhesion/aggregation– NO = 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 / 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

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 = VLDL (TG) LDL HDL

Antioxidant Defense Systems

• 1. Prevent oxidation from being initiated

• 2. Halt oxidation once it has begun

• 3. Repair oxidative damage

Antioxidant Mechanisms

• Antioxidant vitamins (vitamins C, E, carotenoids)

• Flavanoids and other phytochemicals

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

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)

Factors Associated with CVD

• Dietary1. 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

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

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.

Methionine (a.a.)

SAM

SAH

Homocysteine

CH3cysteine

sulfate

1. Norepinephrine2. Guanidinoacetate3. Serotonin4. Serine

1. Epinephrine2. Creatine3. Melatonin4. Choline

Diet

Enzymes B12, Folate

Enzyme B6

Dietary/Lifestyle Prevention/Intervention of Heart Disease

Maintain

Endothelial

Function

Platelet

Activity

Decrease LDL Increase HDL Increase Antioxidants

High Blood Pressure

-3 PUFAs

-6 PUFA

Saturated Fat MUFA/ PUFA

MUFA/ -6 PUFA

Homocysteine

B6, B12, Folic Acid

Phytochemicals Cholesterol -3 PUFAs (fish) Vegetables

Phytochemicals Aspirin -3 oils (fish) Exercise Fruits

Stop smoking Fiber Stop smoking Stop smoking

Trans Fats Body weight if overweight

Fiber

Know Your Lipid Profile

Total Cholesterol < 200 mg/dl

LDL-Cholesterol < 100 mg/dl

HDL-Cholesterol ≥ 60 mg/dl

Triglycerides < 150 mg/dl

Fasting Blood Level Ideal, Healthy Level

Know Your Diabetes, Metabolic Risk

Blood Glucose < 110 mg/dl 110-125 mg/dl ≥ 126 mg/dl

2 hr GTT < 140 mg/dl 140-200 mg/dl > 200 mg/dl

Triglyceride < 150 mg/dl > 150 mg/dlTypically elevated

HDL ≥ 60 mg/dlM < 40 mg/dl

F < 50 mg/dlTypically low

Fasting Healthy Pre-Diabetes Diabetes (Metabolic Syndrome)

The Metabolic Syndrome

Abdominal Obesity

Men

Women

> 40 inch waist

> 35 inch waist

Triglycerides ≥ 150 mg/dL

HDL cholesterol

Men

Women< 40 mg/dL

< 50 mg/dL

Blood Pressure ≥ 130/ 85 mm Hg

Fasting Blood Glucose 110-125 mg/dL

Category Systolic (mm/Hg)Diastolic (mm/Hg)

Normal 120 or less 80 or less

High Normal 130-139 85-89

High Blood Pressure

140 or more 90 or more

Know Your Blood Pressure

Strive for blood pressure of 120/80 or less