Chylomicrons are the least dense and biggest lipoproteins

The lipoproteins get smaller and more dense

Very low density lipoprotein (VLDL)

Low density lipoprotein (LDL)

High density lipoprotein (HDL)

The smaller the lipoprotein the more it migrates during electrophoresis - HDL moves the furthest and chlyomicrons move the least

major core lipid is dietary triacylglycerols

assoc. apoproteins are B-48 (chylomicron marker), C, and E

mechanism of lipid delivery is hydrolysis by lipoprotein lipase

major core lipids - dietary cholesterol esters

apoproteins - B-48 (marker for chylomicron), E

mechanism of lipid delivery is receptor-mediated endocytosis by liver

major core lipid - endogenous triacylglycerols

apoproteins - B-100 (marker for VLDL, IDL, and LDL), C, E

mechanism of lipid delivery - hydrolysis by lipoprotein lipase

major core lipid - endogenous cholesterol esters

apoproteins - B-100 (marker for VLDL,IDL, and LDL), E

mechanism of lipid delivery - receptor-mediated endocytosis by the liver and converted to LDL

major core lipid - endogenous cholesterol esters

apoprotein - B-100 (marker for VLDL, IDL, and LDL)

mechanism of lipid delivery - receptor-mediated endocytosis by liver and other tissues

major core lipid - endogenous cholesterol esters

apoprotein - A

mechanism of lipid delivery - transfer of cholesterol esters to IDL and LDL

Assoc. with HDL

activates LCAT (Lecithin-choleterol acyl transferase)

interacts with ABC (ATP binding cassette protein) transporter

Assoc. with VLDL and LDL

it binds to LDL receptor

assoc. with chlyomicrons, VLDL, and HDL

it activates lipoprotein lipase

assoc. with chylomicrons, VLDL, and HDL

triggers clearance of VLDL and chylomicron remnants

1) intestinal cells secrete nascent TG-rich chlyomicrons (produced primarily from dietary lipids)

2) ApoC-II and apo E are transferred from HDL to nascent CM

3) apoC-II activates lipoprotein lipase and it degrades triacylglycerols in CM

4) ApoC-II is returned to HDL

5) cholesterol ester rich CM remnants bind through apoE to specific receptors on the liver where they are endocytosed

Lipoprotein lipase hydrolyzes the TG of chylomicrons and VLDL, on carbons 1 and 3

The enzyme is located in the walls of blood capillaries of extrahepatic tissues, where it adheres to heparin sulfate on the surface of endothelial cells

Heart lipoprotein lipase has a low km for TG whereas adipose has a km 10 times greater. As plasma [TG] decreases in the transition from the fed to starved state, the heart enzyme remains saturated while the saturation of the adipose enzyme diminishes, thus redirecting uptake of FFA from adipose to the heart.

1) Liver secretes nascent TAG-rich VLDL particles

2) ApoC-II and ApoE are transferred from HDL to VLDL

3) extracellular lipoprotein lipase activated by ApoC-II, degrades TAG in VLDL

4) ApoC-II and ApoE are returned to HDL

5) LDL binds to specific receptors on extrahepatic tissues and on the liver, where they are endocytosed

An enzyme anchored on the surface of liver cells by heparan sulfate that hydrolyzes TG and, to some extent, phospholipids in Chylo and VLDL remnants (IDL) and HDL.

Necessary in the conversion of VLDL remnants to LDL

It occurs by receptor mediated endocytosis

1) LDL binds to receptors in a pit coated by clathrin

2) LDL internalized as intact particles by endocytosis

3) vesicle containing the LDL rapidly loses its clathrin coat and fuses with other vesicles forming larger vesicles called endosomes

4) the pH of the endosome becomes more acidic and the LDL dissociates from its receptors

5) receptors are recycled and the lipoprotein remnants are degraded releasing cholesterol, phospholipids, AA's and FA's

Circulating LDL can bind to cells in the tissue and undergo receptor mediated endocytosis

The eventual release of cholesterol regulates cholesterol synthesis

- HMG CoA reductase activity is decreased (decreasing de novo cholesterol synthesis)

- cholesterol that is not needed immediately is esterified by acyl CoA: cholesterol acyltransfeases (ACAT). It transfers a FA from a fatty acyl CoA derivate to cholesterol producing a cholesterly ester that can be stored in the cell

- ACAT activity is increased by increased intracellular cholesterol

- synthesis of new LDL receptors is lowered by decreased transcription of the gene

HDL serves as a circulating reservoir of ApoC-II (activator of lipoprotein lipase) and ApoE

- it transfers them to VLDL and CM

- it also takes them back

HDL removes free cholesterol from extrahepatic tissues and esterifies it using LCAT (which is activated by apoA-I)

HDL is taken up by the liver through receptor mediated endocytosis and the cholesterol esters are degraded

LCAT (Lecithin-cholesterol acyl transferase): A soluble enzymes that associates with HDL in the circulation.

Activated by apo A1 and catalyzes the formation of cholesterol esters from free cholesterol in HDL, releasing 2-lysoPC. The cholesterol esters sink to the center of the HDL particle.

also known as PCAT (phosphatidylcholine:cholesterol acyltransferase)

elevated CM

severe elevation of TAG

small elevation of cholesterol

small decrease in LDL

-cholesterol molecular defects in lipoprotein lipase and apoC-II

genetic nomenclature - familial chylomicronemia

syndrome frequency - 1/1,000,000 - extremely rare

elevated LDL

no change in TAG

severe elevation of cholesterol

moderate elevation of LDL-cholesterol

premature atherosclerosis

molecular defects in LDL receptor, ApoB-100

genetic nomenclature - familial hypercholesterolemia

frequency - 1/500 - 1/600 - somewhat common

elevated LDL and VLDL

moderate elevation of TAG

severe elevation of cholesterol

moderate elevation of LDL-cholesterol

premature atherosclerosis

unknown molecular defects

genetic nomenclature - familial combined hyperlipidemia

frequency - 1/200 - somewhat common

elevated CM and VLDL remnants

severe elevation of TAG

moderate elevation of cholesterol

slight decrease in LDL-cholesterol

premature atherosclerosis

molecular defect - ApoE

genetic nomenclature - familial dysbetalipoproteinemia

frequency - 1/10,000 - rare

Type II hyperlipidemia or Familial hypercholesterolemia has significant differences between hetero and homo

Freq - hetero 1/500, homo - 1/1,000,000

expression of LDL receptor - hetero - 40-50%, homo - 0-5%

increase in LDL cholesterol - hetero - 2x, homo 5-7x

onset of CAD - hetero - 40-60 yr, homo - 0-30 yr

xanthomas (lipid buildup) - hetero - 75%, homo - 100%

homozygotes have more severe symptoms!

This is an overlap syndrome where a group of metabolic risk factors is seen in one person. 

They include:

Abdominal obesity (excessive fat tissue in and around the abdomen)

Atherogenic dyslipidemia (blood fat disorders - high triglycerides, low HDL cholesterol and high LDL cholesterol - that foster plaque buildups in artery walls)

Elevated blood pressure

Insulin resistance or glucose intolerance (the body can’t properly use insulin or blood sugar)

Prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor - 1 in the blood)

Proinflammatory state (e.g., elevated C-reactive protein in the blood)

This syndrome is increasingly common in the United States; over 50 million Americans may have it. Seen in ~20-30% of premature CHD cases, and other diseases related to plaque buildups in artery walls (e.g., stroke and peripheral vascular disease) and type 2 diabetes.

Some of the factors that can lead to high cholesterol are:

Overweight - Excess weight has been linked with high cholesterol levels.

Heredity - If cholesterol problems or heart disease run in your family, you are at a higher risk for having problems.

Diet - Remember the saying "you are what you eat"? Avoid foods that are high in cholesterol, saturated fat, and trans fat, all of which increase cholesterol levels and your risk of developing heart disease.

Physical activity - Exercise tends to increase HDL levels, which lowers your chance of developing heart disease.

Age - The risk of high cholesterol increases as you get older

ARTERIOSCLEROSIS

*Vascular changes characterized by thickening and loss of elasticity of arterial walls.

*Similar changes in arterioles are known as arteriolosclerosis. It may be seen in patients with chronic hypertension, and, to a lesser degree, as part of the aging process.

ATHEROSCLEROSIS

*A subset of arteriosclerosis

*A disease of large and medium‑sized arteries that result in the progressive accumulation within the intima of smooth muscle cells and lipids.

1.High cholesterol: Increased blood cholesterol leads to increased risk of coronary heart disease.

2.High blood pressure: This increases the heart's workload, and increases the your risk of stroke, heart attack, kidney failure, and congestive heart failure.

3.Smoking: This increases the risk of developing heart disease by 2-4 times.

4.Sedentary lifestyle. Inactivity is a risk factor for coronary heart disease.

5.Obesity: People who have excess body fat - especially if a lot of it is at the waist - are more likely to develop heart disease and stroke even if they have no other risk factors.

6.Diabetes: Having diabetes seriously increases your risk of developing cardiovascular disease. About three-quarters of people with diabetes die from some form of heart or blood vessel disease.

Age: >83% of people who die from coronary heart disease are 65 or older.

Gender: Men have a greater risk of heart attack than women do, and they have attacks earlier in life. The death rate from heart disease for women increases after menopause but it's not as great as men's.

Family history: Those with parents or close relatives with heart disease are more likely to develop it themselves.

Race: Heart disease risk is higher among African Americans, Mexican Americans, American Indians, native Hawaiians, and some Asian Americans compared to Caucasians.

Stress and Type A Behavioural Patterns: These people are twice as likely to exhibit CHD than any other personality type Hemostatic

Factors: High levels of coagulation factor VII and fibrinogen are associated with an increased risk of CHD.

Decrease your low-density lipoprotein (LDL), the "bad" cholesterol that increases the risk of heart disease

Decrease your triglycerides, a type of fat in the blood that also increases the risk of heart disease

Increase your high-density lipoprotein (HDL), the "good" cholesterol that offers protection from heart disease

1.Lose excess pounds: even just 5 to 10 extra pounds can lead to high cholesterol levels.

2. Eat heart-healthy foods: Saturated fats (red meat and dairy products) and trans fat (fried foods and commercial baked items) raise your total cholesterol and LDL cholesterol. Limit cholesterol intake (< 300 mg per day). Select whole grains, fruits and vegetables, which are rich in dietary fiber, and eat foods rich in omega-3 fatty acids, such as salmon, mackerel, walnuts, and almonds.

3. Get some daily exercise, which can reduce cholesterol levels and can help raise HDL levels.

4. Quit smoking, which can improve your HDL cholesterol level, and within just 20 minutes after quitting, your blood pressure decreases.

5. Drink alcohol only in moderation (one or two glasses of wine or beer per day, which is linked with higher levels of HDL cholesterol

*Altoprev (lovastatin) 

Crestor (rosuvastatin) 

Lescol (fluvastatin) 

Lipitor (atorvastatin) 

*Mevacor (lovastatin) 

Pravachol (pravastatin) 

Zocor (simvastatin)

Class of cholesterol drugs that decrease LDL and TAG and slightly increase HDL

Colestid (colestipol) 

Questran (cholestyramine)

Welchol (colesevelam)

Decrease LDL

Niaspan (prescription niacin)

Slo-Niacin (nonprescription niacin)

decrease LDL and TAG

increase HDL

composed of the lowest amount of TAG

and high amount of cholesterol

functions to deliver cholesterol to the liver for elimination

composed of low TAG and

highest amount of cholesterol

functions to deliver cholesterol to the peripheral tissues and liver

composed of high TAG and

low cholesterol

functions to deliver de novo TAG to peripheral tissues

composition - Highest TAG and

lowest cholesterol

functions to deliver dietary TAG to peripheral tissues

*VLDL

Carries triglycerides to peripheral cells

High levels may be associated with increased CHD risk

*LDL

Carries cholesterol to cells

High levels linked to increased CHD risk

Primary target of cholesterol-reducing therapy

*HDL

Removes cholesterol from cells

High HDL considered protective against CHD

HDL >60 mg/dL decreases CHD risk

*Lipoprotein(a)

A complex of LDL and apolipoprotein(a)

Prevents LDL from being taken up by the liver Elevated Lp(a) is an independent risk factor for premature CHD

*Triglycerides

A neutral fat stored in adipose cells

Positively correlated with risk for CHD