Apolipoproteins Lipid Transfer Proteins and Lipoprotein Metabolism 1
Apolipoproteins, Lipid Transfer Proteins, and Lipoprotein Metabolism 1. 2. 3. 4. Apo-B is the major protein contained in chylomicrons and in VLDL, IDL, and LDL particles. A larger Apo-B-100 is associated with VLDL and LDL of hepatic origin, whereas a lesser molecular weight Apo-B-48 species is found in chylomicrons and intestinally derived VLDL. Apo-B-48 is thought to be generated from the same m. RNA as is Apo-B-100. Apo-E is synthesized in liver and is present on all forms of lipoproteins. Modern, 2014
Apolipoproteins, Lipid Transfer Proteins, and Lipoprotein Metabolism � � � The Apo-E gene is polymorphic with three alleles, isoforms E 2, E 3, and E 4; at least three alleles of the Apo-E gene produce six or more possible genotypes that differ in their ability to bind the LDL receptor. Apo-E genotype associates with plasma total and LDL-CH and may be correlated with the incidence of cardiovascular disease Modern, 2014
HDL 1. 2. 3. 4. HDL particles contain Apo-A-I, the crucial structural protein for HDL, as well as Apo-A-II, Apo-A-IV, and Apo-C. Apo-A-I and Apo-A-IV function as activators of lecithin: CH acyltransferase (LCAT) an enzyme that esterifies CH in plasma. Three C apolipoproteins, Apo-C-II, and Apo-C-III, all are synthesized in the liver. Apo-C-II, present in chylomicrons, VLDL, IDL, and HDL, is important in activation of LPL Modern, 2014
1. 2. 3. 4. 5. Apo-E is important in the hepatic clearance of TG depleted chylomicron remnants. Apolipoproteins are critical in the removal of particles from the circulation. LDL is cleared not only from the plasma into liver cells, but also in adipocytes, smooth muscle cells, and fibroblasts through the LDL receptor. Apo-E. Apo-C-III, present in chylomicrons, IDL, and HDL, may inhibit LPL action. Apo-C-II, activating LPL, hydrolyzes VLDL and chylomicron TG. Modern, 2014
1. 2. 3. Formation of HDL also critically depends on apolipoproteins. Free CH taken up by HDL undergoes esterification by the enzyme LCAT and moves to the core of the HDL particle. As HDL becomes enriched with CE, Apo-C -II and Apo-C-III are picked up from other proteins to form three spherical categories of spherical HDL, termed, in order of increasing size and lipid content, HDL 3, HDL 2 a , and HDL 2 b Modern, 2014
Take Advantage of the Newest Blood Tests 1. 2. The standard tests for cholesterol, HDL, LDL, and triglyceride levels only target about 20 percent of all coronary artery disease patients. The other 80 percent can only be identified by differentiating the particle subgroups which make up the total cholesterol figure.
Kind of HDL particles are divided by size and density. There are five different types: � Two kinds of HDL 2, a and b; � Three kinds of HDL 3, a, b, and c. � HDL 2 particles carry away the cholesterol for disposal. � Elevated levels of certain kinds of HDL 3 particles reflect abnormally increased triglyceride content of the HDL particle. � High HDL 3 complements the increased virulence of the high triglyceride containing LDL particles.
1. 2. 3. 4. Apoprotein b , or atherogenic lipoprotein profile (ALP). ALP is the biggest cause of heart disease. The Apoprotein b test measures the number of the LDL particles. This disorder afflicts 50 percent of heart disease patients.
Apoprotein E Isoform 1. 2. 3. is an actual test of the gene determining the activity of the LDL receptor that attaches to the apoproteins found on various lipid particles. The Apoprotein E structure will determine how LDL particles are cleared from the bloodstream, and how diet will affect this clearance. It can affect heart disease risk
High Lipoprotein (a) or Lp(a) 1. 2. 3. 4. Its presence in the blood can interfere with normal clotting dynamics and promote clotting around atherosclerotic plaques. It also more readily oxidizes and migrates into the arterial wall than even the small dense LDL particle. One third of coronary artery disease patients have elevated Lp (a), and such elevations carry a 250 to 300 percent increased risk. This risk is amplified by the presence of high LDL cholesterol levels, LDL subclass b state, elevated hemocysteine, and
High Lipoprotein (a) or Lp(a) 1. 2. 3. 4. An Lp (a) level above 20 indicates a risk factor, and a level of 30 in some populations is equivalent to the danger of a total cholesterol of 240! It is also a factor particularly threatening to people who have recently had their coronary arteries opened by invasive procedures like angioplasty, the opening of a blocked coronary artery by the inflation of a balloon threaded into the blockage. Forcing the artery open like this, while restoring blood flow, also damages the already injured arterial inner wall.
Discover Lp (a) Level The Lp (a) is an LDL particle with an extra protein, the Apoprotein A, attached to it. Here are the normal ranges of Lp(a) Sex Average Level of Highest 10% of the population Male mg/dl 3. 8 mg/dl 18 Female mg/dl 4. 4 mg/dl 21
Determine Your Individual Genetic Risk Profile 1. Apoprotein E Isoform. 2. a family history of premature (before the age of 60) coronary artery disease makes it five times more likely that you too will develop heart disease at an early age. 3. Everyone should have the following tests performed by the age of 20: Total cholesterol, LDL, HDL, triglyceride, LDL subclass, and Apoprotein E Isoform.
� � 1. 2. 3. 4. 5. Find out your LDL level and LDL Subclass What Is An Adequate HDL? Triglyceride level and LDL subclass status are half of the influences of HDL level. High triglyceride levels can cause HDLs to fall. Falling triglycerides may signal a rise in HDLs. A low-fat, high-carbohydrate diet that is not intended to gain or lose weight may cause a fall in HDL levels. You’ve learned that the effect of various diets on LDL, however, is highly variable, depending on subclass and, in some cases, on your Apoprotein E test results.
Low HDL 1. 2. 3. 4. 5. Having a persistently low HDL is a serious problem. If after making all the lifestyle adjustments you can, your HDL is still in the unacceptable range, the two most likely possibilities are that you are an LDL subclass B (more likely), or you have a condition called hypoalphalipoproteinemia, In other words, the problem is in your genes. In the case of resistant low HDL associated with subclass B, the first line medication treatments for subclass B are potent HDL boosters. Niacin is a powerful HDL stimulant, and fibrates will prove particularly helpful if triglycerides are above 200.
Low HDL and the Apoprotein A-I Test 1. 2. 3. 4. 5. The Apoprotein A-I test can be used to confirm the low HDL condition due to Hypo A, which is a genetic disorder, and is very deadly. 40% of people who develop heart disease before the age of sixty have this problem either alone or in combination with other factors. It is believed that Hypo A exists in less than 10 percent of the general population, so it’s uncommon, but not rare. It is present in about 20 percent of all coronary artery disease patients. Fifty percent of the children of an affected parent can be affected, so when this condition is discovered, it is absolutely crucial to go up and down the genetic ladder, testing parents and
What Your "Average" Laboratory Test Doesn’t Tell You About Your HDL 1. 2. 3. 4. 5. As there are with LDL, there are different kinds of HDL. However, their relative significance as atherosclerotic risk factors are not nearly as well understood as are the LDL subtypes. Analogous to the LDL-GGE test, which separates different LDL particles, the HDL-GGE test separate the HDL fraction of cholesterol into two families of particles, HDL 2 and HDL 3. In the Finnish study where men with HDL levels below 42 had over a three times risk of having a heart attack, those with HDL 2 had half the risk of those with HDL 3, and it was found to be even more protective than the total HDL level itself. Thus, HDL 2 seems to be the most important protective factor against coronary artery disease, so much so that a decreased level was more dangerous
What Your "Average" Laboratory Test Doesn’t Tell You About Your HDL 1. 2. 3. 4. 5. 6. 7. 8. Still, there is no general agreement about the exact relative significance of these families of HDL. Some studies have shown that HDL 3 is more important. Nevertheless, there is no debate about the protective value of HDL 2. The major task of the HDL particle is to melt atherosclerotic lesions. HDLs float by in the bloodstream, target a cholesterol deposit down in the lining of the artery wall, and carry it back to the liver for disposal. It’s the HDL 2 s then that are actually bringing the cholesterol away for disposal. This is called reverse cholesterol transport. It is probably the single most important event occurring in your body ensuring longevity---it is the biological antidote to atherosclerosis.
To date, several molecular markers involved in the inflammatory process are being investigated as regards their role in the atherosclerotic process or their association with the pathogenesis of CVD. � Among them, we can point out: 1. Oxidized LDL (ox-LDL); 2. Proinflammatory cytokines such as interleukin 1 (IL-1); 3. Tumor necrosis factor alpha (TNF-alpha); 4. Intercellular adhesion molecules (ICAM-1); 5. Hepatic stimulation proteins such as high. Sensitivity C reactive protein (hs-CRP) 6. Serum amyloid A protein (SAAP); 7. Leukocyte count Erika Maria Gonçalves Campana , Arq Bras Cardiol. Jan 2014; 102(1): 60– 69.
M Öhman Scandinavian Journal of Rheumatology , 2014 Vol. 43, No. 4 , Pages 259 -264 tissue plasminogen activator (t. PA), 2. plasminogen activator inhibitor (PAI)-1, 3. von Willebrand factor (v. WF) is required for platelet adhesion , 4. lipids (cholesterol and triglycerides), apolipoproteins (apo. A 1 and apo. B), 5. lipoprotein(a) [Lp(a)], markers of inflammation: 1. Erythrocyte sedimentation rate (ESR), 2. C-reactive protein (CRP), 3. haptoglobin 1.
Wassef H , Changes in total and central fat mass after a hypocaloric diet associate with changes of apo. C-I in postmenopausal obese women. J Clin Lipidol 2014. Sep-Oct; 8(5): 510 -9. � Plasma apo. C-I, apo. C-III, and apo. E are not associated with adiposity, insulin sensitivity, or inflammation in obese but healthy postmenopausal women. � Post-weight-loss changes of total and central fat mass associate with changes of apo. C-I.
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