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| __NOTOC__
| | #Redirect [[High density lipoprotein physiology]] |
| {{High density lipoprotein}}
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| {{CMG}}; {{AE}} {{AN}}; {{RT}}
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| ==Biochemistry==
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| ===Structure===
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| {| class="wikitable" border="1" style="background:PaleGoldenrod"
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| | '''Lipoprotein'''|| '''Density''' || '''Size'''|| '''% Protein'''|| '''Cholesterol in Plasma'''|| '''Triglyceride in Fasting Plasma'''|| '''Major Apolipoprotein'''
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| |- style="background:LemonChiffon"
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| | '''HDL''' || 1.063 - 1.210 g/mL || 6 - 10 mm || 40 - 55% || 0.9 - 1.6 mmol/L || 0.1 - 0.2 mmol/L || apoA-I, apoA-II
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| |}
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| ''For more information about the biochemistry of all lipoproteins, click '''[[lipoprotein|here]]'''.''
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| Shown below is a a schematic image depicting the structure of the HDL. Note that the inner core is made of triglyceride and cholesterol esters whereas the surface is made of amphiphilic phospholipids along with apolipoproteins.
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| [[Image:HDL-structure.gif|400px|The structure of the HDL: the inner core is made of triglyceride and cholesterol esters whereas the surface is made of amphiphilic phospholipids along with apolipoproteins.]]
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| * HDL are the smallest of the lipoproteins. They are the densest because they contain the highest proportion of [[protein]]. They contain the A class of [[apolipoprotein]]s. Apolipoprotein A-I is the main protein of HDL that remove excess cell [[cholesterol]] and protect against [[atherosclerosis]].<ref name="Mahler-1991">{{Cite journal | last1 = Mahler | first1 = DA. | last2 = Shuhart | first2 = CR. | last3 = Brew | first3 = E. | last4 = Stukel | first4 = TA. | title = Ventilatory responses and entrainment of breathing during rowing. | journal = Med Sci Sports Exerc | volume = 23 | issue = 2 | pages = 186-92 | month = Feb | year = 1991 | doi = | PMID = 2017014 }}</ref>
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| * The liver synthesizes these lipoproteins as complexes of apolipoproteins and phospholipids, which resemble cholesterol-free flattened spherical lipoprotein particles. They are capable of picking up cholesterol from cells they interact with.
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| * A [[Blood plasma|plasma]] enzyme called [[lecithin-cholesterol acyltransferase]] (LCAT) converts the free cholesterol into [[cholesteryl ester]] (a more hydrophobic form of cholesterol) which is then sequestered into the core of the lipoprotein particle eventually making the newly synthesized HDL spherical. They increase in size as they circulate through the bloodstream and incorporate more cholesterol molecules into their structure.
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| * Thus it is the concentration of large HDL particles which more accurately reflects protective action, as opposed to the concentration of total HDL particles.<ref>Kwiterovich PO. The Metabolic Pathways of High-Density Lipoprotein, Low-Density Lipoprotein, and Triglycerides: A Current Review. Am J Cardiol 2000;86(suppl):5L.</ref> This ratio of large HDL to total HDL particles varies widely and is only measured by more sophisticated lipoprotein assays using either [[electrophoresis]], originally developed in the 1970s, or newer [[Nuclear magnetic resonance|nuclear magnetic resonance]] (NMR) spectroscopy which was developed in the 1990s.
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| * HDL particles are not inherently protective. It is only the HDL particles which become the largest (actually picking up and carrying cholesterol) which are protective. There is no reliable relationship between total HDL and large HDL, and more sophisticated analyses which actually measure large HDL, not just total, correlate much better with clinical outcomes.<ref name="pmid23488589">{{cite journal |author=Tran-Dinh A, Diallo D, Delbosc S, ''et al.'' |title=HDL and endothelial protection |journal=[[British Journal of Pharmacology]] |volume= |issue= |pages= |year=2013 |month=March |pmid=23488589 |doi=10.1111/bph.12174 |url=}}</ref>
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| * Many studies have postulated an association between cholesterol efflux from peripheral tissue, and Apo A-I HDL particles, whereas the HDL<sub>3</sub> containing both Apo A-I and A-II are less effective. <ref name="pmid23564081">{{cite journal |author=Yin K, Tang SL, Yu XH, ''et al.'' |title=Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE-/- mice possibly via activated STAT3-mediated upregulation of tristetraprolin |journal=[[Acta Pharmacologica Sinica]] |volume= |issue= |pages= |year=2013 |month=April |pmid=23564081 |doi=10.1038/aps.2013.10 |url=}}</ref><ref name="pmid23426429">{{cite journal |author=Mazer NA, Giulianini F, Paynter NP, Jordan P, Mora S |title=A Comparison of the Theoretical Relationship between HDL Size and the Ratio of HDL Cholesterol to Apolipoprotein A-I with Experimental Results from the Women's Health Study |journal=[[Clinical Chemistry]] |volume= |issue= |pages= |year=2013 |month=March |pmid=23426429 |doi=10.1373/clinchem.2012.196949 |url=}}</ref><ref name="pmid23351584">{{cite journal |author=Kappelle PJ, Gansevoort RT, Hillege HJ, Wolffenbuttel BH, Dullaart RP |title=Common variation in cholesteryl ester transfer protein: relationship of first major adverse cardiovascular events with the apolipoprotein B/apolipoprotein A-I ratio and the total cholesterol/high-density lipoprotein cholesterol ratio |journal=[[Journal of Clinical Lipidology]] |volume=7 |issue=1 |pages=56–64 |year=2013 |month=January |pmid=23351584 |doi=10.1016/j.jacl.2012.05.003 |url=}}</ref>
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| ===HDL Receptors===
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| * [[ABCA1]] transporter: it is expressed in the peripheral tissues, intestine, liver and macrophage.<ref name="Fitzgerald-2010">{{Cite journal | last1 = Fitzgerald | first1 = ML. | last2 = Mujawar | first2 = Z. | last3 = Tamehiro | first3 = N. | title = ABC transporters, atherosclerosis and inflammation. | journal = Atherosclerosis | volume = 211 | issue = 2 | pages = 361-70 | month = Aug | year = 2010 | doi = 10.1016/j.atherosclerosis.2010.01.011 | PMID = 20138281 }}</ref> An increase in intracellular cholesterol content upregulates ABCA1 trnasporter which is responsible for cholesterol efflux from the intracellular pool.<ref name="Schwartz-2000">{{Cite journal | last1 = Schwartz | first1 = K. | last2 = Lawn | first2 = RM. | last3 = Wade | first3 = DP. | title = ABC1 gene expression and ApoA-I-mediated cholesterol efflux are regulated by LXR. | journal = Biochem Biophys Res Commun | volume = 274 | issue = 3 | pages = 794-802 | month = Aug | year = 2000 | doi = 10.1006/bbrc.2000.3243 | PMID = 10924356 }}</ref>
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| * [[ABCG1]] transporter: it is expressed in intestine and macrophage.<ref name="Fitzgerald-2010">{{Cite journal | last1 = Fitzgerald | first1 = ML. | last2 = Mujawar | first2 = Z. | last3 = Tamehiro | first3 = N. | title = ABC transporters, atherosclerosis and inflammation. | journal = Atherosclerosis | volume = 211 | issue = 2 | pages = 361-70 | month = Aug | year = 2010 | doi = 10.1016/j.atherosclerosis.2010.01.011 | PMID = 20138281 }}</ref> ABCG1 is also responsible for [[cholesterol]] efflux. In addition, ABCG1 may facilitate the oxidation of [[plasma membrane]] cholesterol domains.<ref name="Vaughan-2005">{{Cite journal | last1 = Vaughan | first1 = AM. | last2 = Oram | first2 = JF. | title = ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteins. | journal = J Biol Chem | volume = 280 | issue = 34 | pages = 30150-7 | month = Aug | year = 2005 | doi = 10.1074/jbc.M505368200 | PMID = 15994327 }}</ref>
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| * [[Scavenger receptor#Scavenger receptor class B|Scavenger receptor class B type I (SR-BI)]]: are expressed in liver, endotelial cells and macrophages. It participates in reverse cholesterol transport in which extrahepatic cholesterol is delivered to the liver for excretion into bile.<ref name="Brundert-2005">{{Cite journal | last1 = Brundert | first1 = M. | last2 = Ewert | first2 = A. | last3 = Heeren | first3 = J. | last4 = Behrendt | first4 = B. | last5 = Ramakrishnan | first5 = R. | last6 = Greten | first6 = H. | last7 = Merkel | first7 = M. | last8 = Rinninger | first8 = F. | title = Scavenger receptor class B type I mediates the selective uptake of high-density lipoprotein-associated cholesteryl ester by the liver in mice. | journal = Arterioscler Thromb Vasc Biol | volume = 25 | issue = 1 | pages = 143-8 | month = Jan | year = 2005 | doi = 10.1161/01.ATV.0000149381.16166.c6 | PMID = 15528479 }}</ref><ref name="Out-2004">{{Cite journal | last1 = Out | first1 = R. | last2 = Hoekstra | first2 = M. | last3 = Spijkers | first3 = JA. | last4 = Kruijt | first4 = JK. | last5 = van Eck | first5 = M. | last6 = Bos | first6 = IS. | last7 = Twisk | first7 = J. | last8 = Van Berkel | first8 = TJ. | title = Scavenger receptor class B type I is solely responsible for the selective uptake of cholesteryl esters from HDL by the liver and the adrenals in mice. | journal = J Lipid Res | volume = 45 | issue = 11 | pages = 2088-95 | month = Nov | year = 2004 | doi = 10.1194/jlr.M400191-JLR200 | PMID = 15314100 }}</ref> In macrophages it blunts cytokine production.<ref name="Guo-2009">{{Cite journal | last1 = Guo | first1 = L. | last2 = Song | first2 = Z. | last3 = Li | first3 = M. | last4 = Wu | first4 = Q. | last5 = Wang | first5 = D. | last6 = Feng | first6 = H. | last7 = Bernard | first7 = P. | last8 = Daugherty | first8 = A. | last9 = Huang | first9 = B. | title = Scavenger Receptor BI Protects against Septic Death through Its Role in Modulating Inflammatory Response. | journal = J Biol Chem | volume = 284 | issue = 30 | pages = 19826-34 | month = Jul | year = 2009 | doi = 10.1074/jbc.M109.020933 | PMID = 19491399 }}</ref> In endothelial cells it mediates HDL-induced [[endothelial NOS|endothelial nitric oxide synthase (eNOS)]] activation, proliferation, and migration.<ref name="Besler-2011">{{Cite journal | last1 = Besler | first1 = C. | last2 = Heinrich | first2 = K. | last3 = Rohrer | first3 = L. | last4 = Doerries | first4 = C. | last5 = Riwanto | first5 = M. | last6 = Shih | first6 = DM. | last7 = Chroni | first7 = A. | last8 = Yonekawa | first8 = K. | last9 = Stein | first9 = S. | title = Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. | journal = J Clin Invest | volume = 121 | issue = 7 | pages = 2693-708 | month = Jul | year = 2011 | doi = 10.1172/JCI42946 | PMID = 21701070 }}</ref>
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| ===Enzymes Associated with HDL===
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| =====Cholesterol Ester Transfer Protein (CETP)=====
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| * This protein mediates exchange of cholesterol between HDL particles, and [[triglyceride]] rich [[LDL]] and [[VLDL]] in both directions.
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| * It is normally present in both periphery and liver and functions to channel cholesterol to the liver for uptake and metabolism.
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| =====Lecithin-Cholesterol Acyltransferase (LCAT)=====
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| * It is an enzyme that catalyzes the transfer of fatty acyl chain to free [[cholesterol]] which results in [[cholesteryl ester]] formation.<ref>{{Cite journal | last1 = Zechner | first1 = R. | last2 = Kostner | first2 = GM. | last3 = Dieplinger | first3 = H. | last4 = Degovics | first4 = G. | last5 = Laggner | first5 = P. | title = In vitro modification of the chemical composition of human plasma low density lipoproteins: effects of morphology and thermal properties. | journal = Chem Phys Lipids | volume = 36 | issue = 2 | pages = 111-9 | month = Dec | year = 1984 | doi = | PMID = 6532566 }}</ref>
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| * Its role in extracellular cholesterol metabolism may facilitate the uptake of cholesterol from peripheral tissues to liver into HDL particles by maintaining a concentration gradient for the efflux of free cholesterol which may play a major role in reverse cholesterol transport (RCT).<ref name="Ohashi-2005">{{Cite journal | last1 = Ohashi | first1 = R. | last2 = Mu | first2 = H. | last3 = Wang | first3 = X. | last4 = Yao | first4 = Q. | last5 = Chen | first5 = C. | title = Reverse cholesterol transport and cholesterol efflux in atherosclerosis. | journal = QJM | volume = 98 | issue = 12 | pages = 845-56 | month = Dec | year = 2005 | doi = 10.1093/qjmed/hci136 | PMID = 16258026 }}</ref>
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| ==References==
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| {{Reflist|2}}
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| [[Category:Lipid disorders]]
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| [[Category:Cardiology]]
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| [[Category:Lipoproteins]]
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| [[Category:HDLpedia]]
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