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Encyclopedia > Low density lipoprotein

Low-density lipoprotein (LDL) belongs to the lipoprotein particle family. Its size is approx. 22 nm but since LDL particles contain a changing number of fatty acids they actually have a mass and size distribution. Each native LDL particle contains a single apolipoprotein B-100 molecule (Apo B-100, a protein with 4536 amino acid residues) that circles the fatty acids keeping them soluble in the aqueous environment.[1]. A lipoprotein is a biochemical assembly that contains both proteins and lipids. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Phenylalanine is one of the standard amino acids. ...

Contents

Function

Generally, LDL transports cholesterol and triglycerides from the liver and small intestine to cells and tissues which are taking up cholesterol and triglycerides. Cholesterol is a sterol (a combination steroid and alcohol) and a lipid found in the cell membranes of all body tissues, and transported in the blood plasma of all animals. ... Example of an unsaturated fat triglyceride. ...


Role in disease

Because LDLs transport cholesterol to the arteries and can be retained there by arterial proteoglycans starting the formation of plaques, increased levels are associated with atherosclerosis, and thus heart attack, stroke and peripheral vascular disease. This is why cholesterol inside LDL lipoproteins is called bad cholesterol. Still, it is not the cholesterol that is bad; it is instead how and where it is being transported, and in what amounts over time. Section of an artery For other uses, see Artery (disambiguation). ... Proteoglycans represent a special class of glycoprotein that are heavily glycosylated. ... Acute myocardial infarction (AMI or MI), more commonly known as a heart attack, is a disease state that occurs when the blood supply to a part of the heart is interrupted. ... A stroke or cerebrovascular accident (CVA) occurs when the blood supply to a part of the brain is suddenly interrupted by occlusion (an ischemic stroke- approximately 90% of strokes), by hemorrhage (a hemorrhagic stroke - less than 10% of strokes) or other causes. ... In medicine, peripheral artery occlusive disease (PAOD, also known as peripheral vascular disease (PVD) and peripheral artery disease (PAD) is a collator for all diseases caused by the obstruction of large peripheral arteries, which can result from atherosclerosis, inflammatory processes leading to stenosis, an embolism or thrombus formation. ...


Increasing evidence has revealed that the concentration and size of the LDL particles more powerfully relates to the degree of atherosclerosis progression than the concentration of cholesterol contained within all the LDL particles[citation needed] . The healthiest pattern, though relatively rare, is to have small numbers of large LDL particles and no small particles. Having small LDL particles, though common, is an unhealthy pattern; high concentrations of small LDL particles (even though potentially carrying the same total cholesterol content as a low concentration of large particles) correlates with much faster growth of atheroma, progression of atherosclerosis and earlier and more severe cardiovascular disease events and death. In pathology, an atheroma (plural: atheromata) is an accumulation and swelling (-oma) in artery walls that is made up of cells, or cell debris, that contain lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. ...


LDL is formed as VLDL lipoproteins lose triglyceride through the action of lipoprotein lipase (LPL) and become smaller and denser, containing a higher proportion of cholesterol. Very Low Density Lipoprotein (VLDL) is a lipoprotein subclass. ... Lipoprotein lipase (EC 3. ...


A hereditary form of high LDL is familial hypercholesterolemia (FH). Increased LDL is termed hyperlipoproteinemia type II (after the dated Fredrickson classification). In medicine, familial hypercholesterolemia is a rare disease characterised by very high LDL cholesterol and early cardiovascular disease running in families. ... The second type of high blood lipids (cholesterol) in the (dated) Fredrickson classification, which is determided by lipoprotein electrophoresis. ... Hyperlipidemia, hyperlipoproteinemia or dyslipidemia is the presence of elevated or abnormal levels of lipids and/or lipoproteins in the blood. ...


LDL poses a risk for cardiovascular disease when it invades the endothelium and becomes oxidized since the oxidized form is more easily retained by the proteoglycans. A complex set of biochemical reactions regulates the oxidation of LDL, chiefly stimulated by presence of free radicals in the endothelium. Nitric oxide down-regulates this oxidation process catalyzed by L-arginine. Correspondingly when there are high levels of asymmetric dimethylarginine in the endothelium, production of nitric oxide is inhibited and more LDL oxidation occurs.Citations required for this paragraph Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... To oxidize an element or a compound is to increase its oxidation number. ... Arginine (Arg) is an α-amino acid. ... Molecular structure of ADMA Asymmetric dimethylarginine (ADMA) is a naturally occurring chemical found in blood plasma. ...


Importance of antioxidants

Blood fats such as low-density lipoprotein (LDL) cholesterol also suffer the wrath of oxidative stress. Research suggests that, despite its reputation as the "bad" kind of cholesterol, LDL itself is harmless. Only when oxidized--that is, only when it gives up an electron to a free radical--does LDL cause the arterial hardening and clogging that lay the groundwork for heart attack and stroke. This explains why about half of all people with elevated total cholesterol and LDL cholesterol never experience heart attacks: Their LDL has not undergone oxidation. How do some folks manage to avoid oxidative stress? First, they minimize their free radical exposure. Second, they increase their antioxidant protection. Both strategies may be helpful in preventing atherosclerosis.[1]


LDL import to the cell

When a cell requires cholesterol, it synthesises the necessary LDL receptors, and inserts them into the plasma membrane. The LDL receptors diffuse freely until they associate with clathrin coated pits. LDL particles in the blood stream bind to these extracellular LDL receptors. The clathrin coated pits then form vesicles which are endocytosed into the cell. Clathrin is a protein that is the major constituent of the coat of the coated pits and coated vesicles formed during endocytosis of materials at the surface of cells. ...


After the clathrin coat is shed the vesicles deliver the LDL and their receptors to early endosomes, onto late endosomes to lysosomes. Here the cholesterol esters in the LDL are hydrolysed. The LDL receptors are recycled back to the plasma membrane. In biology an endosome is an endocytotic vesicle derived from the plasma membrane. ...


Recommended range; changing targets

The American Heart Association, NIH and NCEP provide a set of guidelines for fasting LDL-Cholesterol levels, estimated or measured, and risk for heart disease. As of 2003, these guidelines were: The American Heart Association (AHA) is a non-profit organization in the United States that fosters appropriate cardiac care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke. ... The National Institutes of Health (NIH) is the primary agency of the United States government responsible for medical research. ... The National Cholesterol Education Program is a program managed by the National Heart, Lung and Blood Institute, a division of the National Institutes of Health. ... This article or section does not adequately cite its references or sources. ...

Level mg/dL Level mmol/L Interpretation
<100 <2.6 Optimal LDL cholesterol, corresponding to reduced, but not zero, risk for heart disease
100 to 129 2.6 to 3.3 Near optimal LDL level
130 to 159 3.3 to 4.1 Borderline high LDL level
160 to 189 4.1 to 4.9 High LDL level
>190 >4.9 Very high LDL level, corresponding to highest increased risk of heart disease

These guidelines were based on a goal of presumably decreasing death rates from cardiovascular disease to less than 2 to 3%/year or less than 20 to 30%/10 years. Also notice that 100 is not considered optimal, but less than 100, unspecified how much less. The U.S. National Prototype Kilogram, which currently serves as the primary standard for measuring mass in the U.S. It was assigned to the United States in 1889 and is periodically recertified and traceable to the primary international standard, The Kilogram, held at the Bureau International des Poids et... The litre or liter (see spelling differences) is a unit of volume. ... The mole (symbol: mol) is the SI base unit that measures an amount of substance. ...


Over time, with more clinical research, these recommended levels keep being reduced because LDL reduction, including to abnormally low levels has been the most effective strategy for reducing cardiovascular death rates in large double blind, randomized clinical trials; far more effective than coronary angioplasty/stenting or bypass surgery. The Double blind method is an important part of the scientific method, used to prevent research outcomes from being influenced by the placebo effect or observer bias. ...


For instance, for people with known atherosclerosis diseases, the 2004 updated American Heart Association, NIH and NCEP recommendations are for LDL levels to be lowered to less than 70 mg/dL, unspecified how much lower. It has been estimated from the results of multiple human pharmacologic LDL lowering trials that LDL should be lowered to about 50 to reduce cardiovascular event rates to near zero. For reference, from longitudinal population studies following progression of atherosclerosis related behaviors from early childhood into adulthood, it has been discovered that the usual LDL in childhood, before the development of fatty streaks is about 35 mg/dL. However, all the above values refer to chemical measures of lipid/cholesterol concentration within LDL, not LDLipoprotein concentrations, probably not the better approach. The American Heart Association (AHA) is a non-profit organization in the United States that fosters appropriate cardiac care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke. ... Fatty streak is the term generally given to the earliest stages of atheroma, as viewed at autopsy, looking at the inner surface of arteries, without magnification. ...


Measurement methods

Chemical measures of lipid concentration have long been the most-used clinical measurement, not because they have the best correlation with individual outcome, but because these lab methods are less expensive and more widely available. However, there is increasing evidence and recognition of the value of more sophisticated measurements. Specifically, LDL particle number (concentration), and to a lesser extent size, have shown much tighter correlation with atherosclerotic progression and cardiovascular events than is obtained using chemical measures of total LDL concentration contained within the particles. LDL cholesterol concentration can be low, yet LDL particle number high and cardiovascular events rates are high. Alternatively, LDL cholesterol concentration can be relatively high, yet LDL particle number low and cardiovascular events are also low. If LDL particle concentration is tracked against event rates, many other statistical correlates of cardiovascular events, such as diabetes mellitus, obesity and smoking, lose much of their additive predictive power. For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ...


LDL subtype patterns

LDL particles actually vary in size and density, and studies have shown that a pattern that has more small dense LDL particles—called "Pattern B"—equates to a higher risk factor for coronary heart disease (CHD) than does a pattern with more of the larger and less dense LDL particles ("Pattern A"). This is because the smaller particles are more easily able to penetrate the endothelium. "Pattern I", meaning "intermediate", indicates that most LDL particles are very close in size to the normal gaps in the endothelium (26 nm). This article or section does not adequately cite its references or sources. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ...


The correspondence between Pattern B and CHD has been suggested by some in the medical community to be stronger than the correspondence between the LDL number measured in the standard lipid profile test. Tests to measure these LDL subtype patterns have been more expensive and not widely available, so the common lipid profile test has been used more commonly.


The lipid profile does not measure LDL level directly but instead estimates it via the Friedewald equation [1] using levels of other cholesterol such as HDL: High-density lipoproteins (HDL) form a class of lipoproteins, varying somewhat in their size (8–11 nm in diameter), that carry cholesterol from the bodys tissues to the liver. ...

textit{LDL-C} approx textit{Total cholesterol} - textit{HDL-C} - 0.20 * textit{Total triglycerides}

In mg/dl: LDL cholesterol = total cholesterol – HDL cholesterol – (0.2 × triglycerides)
In mmol/l: LDL cholesterol = total cholesterol – HDL cholesterol – (0.45 × triglycerides)


There are limitations to this method, most notably that samples must be obtained after a 12 to 14 h fast and that LDL-C cannot be calculated if plasma triglyceride is >4.52 mmol/L (400 mg/dL). Even at LDC-L levels 2.5 to 4.5 mmol/L, this formula is considered to be inaccurate (see Sniderman et al., [2]).


If both total cholesterol and triglyceride levels are elevated then a modified formulat may be used


LDL-C = Total-C HDL-C (0.16 x Trig)


This formula provides an approximation with fair accuracy for most people, assuming the blood was drawn after fasting for about 14 hours or longer. (However, the concentration of LDL particles, and to a lesser extent their size, has far tighter correlation with clinical outcome than the content of cholesterol with the LDL particles, even if the LDL-C estimation is about correct.)


There has also been noted a correspondence between higher triglyceride levels and higher levels of smaller, denser LDL particles and alternately lower triglyceride levels and higher levels of the larger, less dense LDL. [3] [4].


However, cholesterol and lipid assays, as outlined above were never promoted because they worked the best to identify those more likely to have problems, but simply because they used to be far less expensive, by about 50 fold, than measured lipoprotein particle concentrations and subclass analysis. With continued research, decreasing cost, greater availability and wider acceptance of other "lipoprotein subclass analysis" assay methods, including NMR spectroscopy, research studies have continued to show a stronger correlation between human clinically obvious cardiovascular event and quantitatively measured particle concentrations. It has been suggested that NMR Data Processing be merged into this article or section. ...


Citations

  1. ^ Segrest, J. P. et al (September 2001). "Structure of apolipoprotein B-100 in low density lipoproteins". Journal of Lipid Research 42: 1346-1367. 

References

[1] [5]

  • Adult Treatment Panel III Full Report
  • ATP III Update 2004
  • Cromwell WC, Otvos JD (2004). "Low-density lipoprotein particle number and risk for cardiovascular disease". Curr Atheroscler Rep 6 (5): 381-7. PMID 15296705. 
  • O'Keefe JH Jr, Cordain L, Harris WH, Moe RM, Vogel R (2004). "Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal". J Am Coll Cardiol 43 (11): 2142-6. PMID 15172426. 

See also


  Results from FactBites:
 
Low density lipoprotein - Wikipedia, the free encyclopedia (1028 words)
Low-density lipoprotein (LDL) refers to a class and range of lipoprotein particles, varying in their size and contents, which carry cholesterol in the blood and around the body, for use by cells.
Because LDL transports cholesterol to the arteries, increased levels are associated with atherosclerosis, and thus myocardial infarctions, strokes and peripheral vascular disease.
LDL is formed as VLDL lipoproteins, which lose triglyceride through the action of lipoprotein lipase (LPL), and become smaller and denser containing a higher proportion of cholesterol.
MedlinePlus Medical Encyclopedia: LDL (830 words)
LDL is a test that measures the amount of low-density lipoprotein (LDL) cholesterol in blood serum.
The main function of LDL seems to be to carry cholesterol to various tissues throughout the body.
LDL is sometimes referred to as "bad" cholesterol, because elevated levels of LDL correlate most directly with coronary heart disease.
  More results at FactBites »

 
 

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