Lipoproteins



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Lipoproteins

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 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

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

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
  • Shifting to a
  • pro-coagulant, pro-thrombotic surface
  • Increased:
  • pro-inflammatory
  • molecules:
  • MCP-1
  • TNF
  • 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

    • • 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.
  • Methionine (a.a.)
  • SAM
  • SAH
  • Homocysteine
  • CH3
  • cysteine
  • sulfate
  • 1. Norepinephrine
  • 2. Guanidinoacetate
  • 3. Serotonin
  • 4. Serine
  • 1. Epinephrine
  • 2. Creatine
  • 3. Melatonin
  • 4. 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)
  • 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/dl
  • Typically elevated
  • HDL
  • ≥ 60 mg/dl
  • M < 40 mg/dl
  • F < 50 mg/dl
  • Typically low
  • Fasting Healthy Pre-Diabetes Diabetes
  • (Metabolic Syndrome)

The Metabolic Syndrome

  • Abdominal Obesity
  • Men
  • Women
  • 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

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

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