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LDL redirects here. For other uses, see LDL (disam- direct measurements of LDL-particles and actual rates of
biguation).
atherosclerosis progression.
Direct LDL measurements are also available and better
reveal individual issues but are less often promoted or
done due to slightly higher costs and being available from
only a couple of laboratories in the United States. In
2008, the ADA and ACC recognized direct LDL particle
measurement by NMR as superior for assessing individual risk of cardiovascular events.[5]
2 Biochemistry
2.1 Structure
Each native LDL particle enables emulsication, i.e. surrounding/packaging all fatty acids being carried, enabling
these fats to move around the body within the water outside cells. Each particle contains a single apolipoprotein
B-100 molecule (Apo B-100, a protein that has 4536
amino acid residues and a mass of 514 kDa), along with
80 to 100 additional ancillary proteins. Each LDL has
a highly hydrophobic core consisting of polyunsaturated
fatty acid known as linoleate and hundreds to thousands
(about 1500 commonly cited as an average) esteried and
non-esteried cholesterol molecules. This core also carries varying numbers of triglycerides and other fats and
is surrounded by a shell of phospholipids and unesteried cholesterol, as well as the single copy of Apo B-100.
LDL particles are approximately 22 nm (0.00000087 in.)
in diameter and have a mass of about 3 million daltons.
Since LDL particles contain a variable and changing
number of fatty acid molecules, there is a distribution
of LDL particle mass and size.[6] Determining the structure of LDL has been a tough task because of its heterogeneous structure. The structure of LDL at human
body temperature in native condition, with a resolution
of about 16 Angstroms using cryo-electron microscopy,
has been recently described.[7]
Testing
classication).
Keep in mind that LDL-C is not a measurement of actual LDL particles; LDL-C is only an estimate (not measured from the individuals blood sample) of how much
cholesterol is being transported by all LDL particles; either a smaller concentration of large particles or a high
concentration of small particles. Also keep in mind
that LDL particles carry many fat molecules (typically
3,000 to 6,000 fat molecules per LDL particle); this includes cholesterol, triglycerides, phospholipids and others. Thus even if the hundreds to thousands of cholesterol
molecules within an average LDL particle were measured, this does not reect the other fat molecules or even
the number of LDL particles.
3.2.1 Pharmaceutical
Statins reduce high levels of LDL particles by inhibiting the enzyme HMG-CoA reductase in cells,
the rate-limiting step of cholesterol synthesis. To
compensate for the decreased cholesterol availability, synthesis of hepatic LDL receptors is increased,
resulting in an increased clearance of LDL particles
from the blood.
Ezetimibe reduces intestinal absorption of cholesterol, thus can reduce LDL particle concentrations
when combined with statins.[18]
3.3
Importance of antioxidants
PCSK9 inhibitors, in phase 3 clinical trials, by several companies, appear to be far more eective for
LDL reduction than the statins, even statins at high
dose.
Niacin (B3 ), lowers LDL by selectively inhibiting hepatic diacyglycerol acyltransferase 2, reducing
triglyceride synthesis and VLDL secretion through a
receptor HM74[19] and HM74A or GPR109A.[20]
Several CETP inhibitors have been researched to
improve HDL concentrations, but so far, despite
dramatically increasing HDL-C, have not had a consistent track record in reducing atherosclerosis disease events. Some have increased mortality rates
compared with placebo.
3
activity.[26] While glucagon production is stimulated
by dietary protein ingestion, insulin production is
stimulated by dietary carbohydrate. The rise of insulin is, in general, determined by the digestion of
carbohydrates into glucose and subsequent increase
in serum glucose levels. In non-diabetics, glucagon
levels are very low when insulin levels are high; however, those who have become diabetic no longer suppress glucagon output after eating.
A ketogenic diet may have similar response to taking
niacin (lowered LDL and increased HDL) through
beta-hydroxybutyrate, a ketone body, coupling the
niacin receptor (HM74A).[20]
Lowering the blood lipid concentration of
triglycerides helps lower the concentration of
small LDL particles, because fatty-acid rich VLDL
particles convert in the bloodstream into small
dense LDL particles.
5
coronary heart disease.[42]
ticle concentrations
There are several competing methods for measurement
of lipoprotein particle concentrations and size. The evidence is that the NMR methodology (developed, automated & greatly reduced in costs while improving accuracy as pioneered by Jim Otvos and associates) results
in a 22-25% reduction in cardiovascular events within
just a single year,[44] contrary to the longstanding claims
by many in the medical industry that the superiority
over existing methods was weak, even by statements of
some proponents.[45] Direct LDL particle measurement
by NMR was mentioned by the ADA and ACC, in a 28
March 2008 joint consensus statement,[46] as having advantages for predicting individual risk of atherosclerosis
disease events, but the statement noted that the test is
less widely available (single vendor which accepts sample
from world-wide), is more expensive (about $80.00 US
without insurance coverage) and it is "...unclear whether
LDL particle size measurements add value to measurement of LDL particle concentration, an issue which LipoScience consultants also tend to agree with (yet also
has little to do with the value of measuring LDL particles
vs. ApoB vs. cholesterol). Since the later 1990s, because of the development of NMR measurements, it has
been possible to clinically measure lipoprotein particles
at lower cost [under $100 US (including shipping) & deceasing; versus the previous costs of >$400 to >$5,000]
and higher accuracy. There are also other (less expensive) homogeneous assays for LDL, however most only
estimate LDL.
Using NMR, as pioneered by researcher Jim Otvos and
the North Carolina State University academic research
spino company LipoScience, the total LDL particle
concentrations, in nmol/L plasma, are typically subdivided by percentiles referenced to the 5,382 men and
women, not on any lipid medications, who are participating in the MESA trial.[47]
6 See also
Catechin
Cholesterol
Lysosomal acid lipase deciency
Cholesteryl ester storage disease
Coenzyme Q10
Flavonoid
Glutathione
Health eects of tea
High density lipoprotein
LDL receptor
Lipid prole
Lipoprotein(a)
Lipoprotein-X
Melatonin
Polyphenol antioxidant
Saturated fat
Stanol ester
Sterol ester
Triglyceride
Vitamin A
Vitamin C
5.1
Optimal ranges
The LDL particle concentrations are typically categorized by percentiles, <20%, 2050%, 50th80th%, 80th
95% and >95% groups of the people participating and being tracked in the MESA trial, a medical research study
sponsored by the United States National Heart, Lung, and
Blood Institute.
The lowest incidence of atherosclerotic events over time
occurs within the <20% group, with increased rates for
Vitamin E
7 Footnotes
[1] Dashti M, Kulik W, Hoek F, Veerman EC, Peppelenbosch MP, Rezaee F. (2011). A phospholipidomic analysis of all dened human plasma lipoproteins.. Sci Rep.
1 (139). doi:10.1038/srep00139. PMC 3216620. PMID
22355656.
[2] Dashty M, Motazacker MM, Levels J, de Vries M, Mahmoudi M, Peppelenbosch MP, Rezaee F. (2014). Proteome of human plasma very low-density lipoprotein and
low-density lipoprotein exhibits a link with coagulation
and lipid metabolism.. Thromb Haemost. 23 (111): 518
530. doi:10.1160/TH13-02-0178. PMID 24500811.
[3] http://www.nejm.org/doi/full/10.1056/
NEJM198705283162204
[4] LDL and HDL Cholesterol: Whats Bad and Whats
Good?
7 FOOTNOTES
[15] http://www.nhlbi.nih.gov/health-pro/guidelines/current/
cholesterol-guidelines/
[16] https://www.acli.com/Events/Documents/Tue22812%
20-%20Lipidology%20-%20Pamela%20Morris.pdf
[17] Consumer Reports; Drug Eectiveness Review Project
(March 2013), Evaluating statin drugs to treat High
Cholesterol and Heart Disease: Comparing Eectiveness,
Safety, and Price, Best Buy Drugs (Consumer Reports):
9, retrieved 27 March 2013, which cites
United States Department of Health and Human
Services; National Heart, Lung, and Blood Institute;
National Institutes of Health (June 2005). NHLBI,
High Blood Cholesterol: What You Need to Know.
nhlbi.nih.gov. Retrieved 27 March 2013.
[18]
[8] http://onlinelibrary.wiley.com/doi/10.1002/clc.
4960280510/pdf
[9] http://www.msnbc.msn.com/id/
35058896/ns/health-heart_health/t/
bad-cholesterol-its-not-what-you-think/#.T4Gkub_
Owrg[]
[10] Superko HR, Nejedly M, Garrett B (2002). Small LDL
and its clinical importance as a new CAD risk factor: a
female case study. Progress in Cardiovascular Nursing
17 (4): 16773. doi:10.1111/j.0889-7204.2002.01453.x.
PMID 12417832.
[11] Warnick GR, Knopp RH, Fitzpatrick V, Branson L (January 1990). Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints. Clinical Chemistry 36 (1): 159. PMID 2297909.
[12] Otvos J (June 1999). Measurement of triglyceriderich lipoproteins by nuclear magnetic resonance spectroscopy.
Clin Cardiol 22 (6 Suppl): II217.
doi:10.1002/clc.4960221405. PMID 10376193.
[21] WHO cooperative trial on primary prevention of ischemic heart disease with clobrate to lower serum
cholesterol: nal mortality follow-up. Report of the Committee of Principal Investigators. Lancet 2 (8403): 600
4. September 1984. PMID 6147641.
[22] http://www.rxabbott.com/pdf/trilipix_pi.pdf
[23] Song, B.L.; DeBose-Boyd, R.A. (2006).
InsigDependent Ubiquitination and Degradation of 3Hydroxy-3-Methylglutaryl Coenzyme A Reductase
Stimulated by Delta- and Gamma-Tocotrienols.
J. Biol.
Chem.
281 (35):
2505425601.
doi:10.1074/jbc.M605575200. PMID 16831864.
[24] European Food Safety Authority, Journal (2010).
Scientic opinion on the substantiation of health claims
related to plant sterols and plant stanols and maintenance
of normal blood cholesterol concentrations.
[25] Demonty, I; Ras, RT, van der Knaap, HC, Duchateau,
GS, Meijer, L, Zock, PL, Geleijnse, JM, Trautwein,
EA (Feb 2009). Continuous dose-response relationship of the LDL-cholesterol-lowering eect of phytosterol intake.. The Journal of nutrition 139 (2): 27184.
doi:10.3945/jn.108.095125. PMID 19091798.
[26] Regulation of Cholesterol Synthesis
[13] http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/
mb2/part1/lipoprot.htm
[27] http://www.omegalife.com.au/garcinia-cambogia
[14] Peterson MM, Mack JL, Hall PR, et al. (December 2008).
Apolipoprotein B Is an innate barrier against invasive
Staphylococcus aureus infection. Cell Host & Microbe
4 (6): 55566. doi:10.1016/j.chom.2008.10.001. PMC
2639768. PMID 19064256.
[28] Inhibition of in vitro human LDL oxidation by phenolic antioxidants from grapes and wines. Teissedre, P.L.
: Frankel, E.N. : Waterhouse, A.L. : Peleg, H. : German,
J.B. J-sci-food-agric. Sussex : John Wiley : & : Sons
Limited. Jan 1996. v. 70 (1) p. 55-61.
8 External links
Fat (LDL) Degradation: PMAP The Proteolysis
Map-animation
Adult Treatment Panel III Full Report
ATP III Update 2004
O'Keefe JH, Cordain L, Harris WH, Moe RM, Vogel R (June 2004). Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and
physiologically normal. Journal of the American College of Cardiology 43 (11): 21426.
doi:10.1016/j.jacc.2004.03.046. PMID 15172426.
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