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
Chylomicron
Triglycerides
3 Fatty Acids
Adipose
(storage)
Glycerol
Skeletal
Muscle
(energy)
Heart
(energy)
Blood
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
VLDL
Triglycerides
3 Fatty Acids
Adipose
(storage)
Skeletal
Muscle
(energy)
Glycerol
Heart
(energy)
Blood
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 Endothelium
produces:
 PGI2
 NO
Maintaining an
anti-coagulant,
anti-thrombotic
surface
A Dysfunctional Endothelium
has decreased:
 PGI2
 NO
Increased:
pro-inflammatory
molecules:
MCP-1
TNFa
VCAM-1
Shifting to a
pro-coagulant, prothrombotic surface
Pro-Inflammatory Molecules
• Chemokines = monocyte chemoattractant protein 1
(MCP-1)
• Inflammatory cytokines = tumor necrosis factor a
(TNFa)
• 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
– Proteins
- carbohydrates
- 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
• 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
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.
Diet
Methionine (a.a.)
Enzymes
B12, Folate
Homocysteine
SAM
Enzyme
B6
cysteine
CH3
SAH
sulfate
1. Norepinephrine
2. Guanidinoacetate
3. Serotonin
4. Serine
1. Epinephrine
2. Creatine
3. Melatonin
4. Choline
Dietary/Lifestyle Prevention/Intervention of Heart
Disease
Maintain
Endothelial
Function
Platelet
Activity
Decrease LDL
Increase HDL
Increase
Antioxidants
 High Blood
Pressure
 w-3 PUFAs
 w -6 PUFA
 Saturated Fat
 MUFA/  PUFA
 MUFA/
 w -6 PUFA
 Homocysteine
B6, B12, Folic Acid
 Phytochemicals
 Cholesterol
 w-3 PUFAs (fish)
Vegetables
Phytochemicals
Aspirin
 w-3 oils (fish)
 Exercise
Fruits
 Fiber
Stop smoking
Stop smoking
 Trans Fats
Body weight if
overweight
Stop smoking
 Fiber
Know Your Lipid Profile
Fasting Blood Level
Ideal, Healthy Level
Total Cholesterol
< 200 mg/dl
LDL-Cholesterol
< 100 mg/dl
HDL-Cholesterol
≥ 60 mg/dl
Triglycerides
< 150 mg/dl
Know Your Diabetes, Metabolic Risk
Fasting
Healthy
Pre-Diabetes
Diabetes
(Metabolic Syndrome)
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/dl
Typically elevated
≥ 60 mg/dl
M < 40 mg/dl
F < 50 mg/dl
Typically low
HDL
The Metabolic Syndrome
Abdominal Obesity
Men
Women
Triglycerides
> 40 inch waist
> 35 inch waist
≥ 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
Know Your Blood Pressure
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
Strive for blood pressure of 120/80 or less