High density lipoprotein physiology: Difference between revisions
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====Anti-coagulant Funtions==== | ====Anti-coagulant Funtions==== | ||
HDL has the ability to inhibit platelet activation and aggregation by directly inhibiting platelet activation,<ref name="Calkin-2009">{{Cite journal | last1 = Calkin | first1 = AC. | last2 = Drew | first2 = BG. | last3 = Ono | first3 = A. | last4 = Duffy | first4 = SJ. | last5 = Gordon | first5 = MV. | last6 = Schoenwaelder | first6 = SM. | last7 = Sviridov | first7 = D. | last8 = Cooper | first8 = ME. | last9 = Kingwell | first9 = BA. | title = Reconstituted high-density lipoprotein attenuates platelet function in individuals with type 2 diabetes mellitus by promoting cholesterol efflux. | journal = Circulation | volume = 120 | issue = 21 | pages = 2095-104 | month = Nov | year = 2009 | doi = 10.1161/CIRCULATIONAHA.109.870709 | PMID = 19901191 }}</ref><ref name="Lerch-1998">{{Cite journal | last1 = Lerch | first1 = PG. | last2 = Spycher | first2 = MO. | last3 = Doran | first3 = JE. | title = Reconstituted high density lipoprotein (rHDL) modulates platelet activity in vitro and ex vivo. | journal = Thromb Haemost | volume = 80 | issue = 2 | pages = 316-20 | month = Aug | year = 1998 | doi = | PMID = 9716159 }}</ref> downregulates thromboxane A2 synthesis,<ref name="Brill-2011">{{Cite journal | last1 = Brill | first1 = A. | last2 = Fuchs | first2 = TA. | last3 = Chauhan | first3 = AK. | last4 = Yang | first4 = JJ. | last5 = De Meyer | first5 = SF. | last6 = Köllnberger | first6 = M. | last7 = Wakefield | first7 = TW. | last8 = Lämmle | first8 = B. | last9 = Massberg | first9 = S. | title = von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. | journal = Blood | volume = 117 | issue = 4 | pages = 1400-7 | month = Jan | year = 2011 | doi = 10.1182/blood-2010-05-287623 | PMID = 20959603 }}</ref> increases the synthesis of prostacyclin,<ref name="Fleisher-1982">{{Cite journal | last1 = Fleisher | first1 = LN. | last2 = Tall | first2 = AR. | last3 = Witte | first3 = LD. | last4 = Miller | first4 = RW. | last5 = Cannon | first5 = PJ. | title = Stimulation of arterial endothelial cell prostacyclin synthesis by high density lipoproteins. | journal = J Biol Chem | volume = 257 | issue = 12 | pages = 6653-5 | month = Jun | year = 1982 | doi = | PMID = 7045092 }}</ref> and lowers the expression of tissue factor which is required in the coagulation process.<ref name="Viswambharan-2004">{{Cite journal | last1 = Viswambharan | first1 = H. | last2 = Ming | first2 = XF. | last3 = Zhu | first3 = S. | last4 = Hubsch | first4 = A. | last5 = Lerch | first5 = P. | last6 = Vergères | first6 = G. | last7 = Rusconi | first7 = S. | last8 = Yang | first8 = Z. | title = Reconstituted high-density lipoprotein inhibits thrombin-induced endothelial tissue factor expression through inhibition of RhoA and stimulation of phosphatidylinositol 3-kinase but not Akt/endothelial nitric oxide synthase. | journal = Circ Res | volume = 94 | issue = 7 | pages = 918-25 | month = Apr | year = 2004 | doi = 10.1161/01.RES.0000124302.20396.B7 | PMID = 14988229 }}</ref> | HDL has the ability to inhibit platelet activation and aggregation by directly inhibiting platelet activation,<ref name="Calkin-2009">{{Cite journal | last1 = Calkin | first1 = AC. | last2 = Drew | first2 = BG. | last3 = Ono | first3 = A. | last4 = Duffy | first4 = SJ. | last5 = Gordon | first5 = MV. | last6 = Schoenwaelder | first6 = SM. | last7 = Sviridov | first7 = D. | last8 = Cooper | first8 = ME. | last9 = Kingwell | first9 = BA. | title = Reconstituted high-density lipoprotein attenuates platelet function in individuals with type 2 diabetes mellitus by promoting cholesterol efflux. | journal = Circulation | volume = 120 | issue = 21 | pages = 2095-104 | month = Nov | year = 2009 | doi = 10.1161/CIRCULATIONAHA.109.870709 | PMID = 19901191 }}</ref><ref name="Lerch-1998">{{Cite journal | last1 = Lerch | first1 = PG. | last2 = Spycher | first2 = MO. | last3 = Doran | first3 = JE. | title = Reconstituted high density lipoprotein (rHDL) modulates platelet activity in vitro and ex vivo. | journal = Thromb Haemost | volume = 80 | issue = 2 | pages = 316-20 | month = Aug | year = 1998 | doi = | PMID = 9716159 }}</ref> downregulates thromboxane A2 synthesis,<ref name="Brill-2011">{{Cite journal | last1 = Brill | first1 = A. | last2 = Fuchs | first2 = TA. | last3 = Chauhan | first3 = AK. | last4 = Yang | first4 = JJ. | last5 = De Meyer | first5 = SF. | last6 = Köllnberger | first6 = M. | last7 = Wakefield | first7 = TW. | last8 = Lämmle | first8 = B. | last9 = Massberg | first9 = S. | title = von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. | journal = Blood | volume = 117 | issue = 4 | pages = 1400-7 | month = Jan | year = 2011 | doi = 10.1182/blood-2010-05-287623 | PMID = 20959603 }}</ref> increases the synthesis of prostacyclin,<ref name="Fleisher-1982">{{Cite journal | last1 = Fleisher | first1 = LN. | last2 = Tall | first2 = AR. | last3 = Witte | first3 = LD. | last4 = Miller | first4 = RW. | last5 = Cannon | first5 = PJ. | title = Stimulation of arterial endothelial cell prostacyclin synthesis by high density lipoproteins. | journal = J Biol Chem | volume = 257 | issue = 12 | pages = 6653-5 | month = Jun | year = 1982 | doi = | PMID = 7045092 }}</ref> and lowers the expression of tissue factor which is required in the coagulation process.<ref name="Viswambharan-2004">{{Cite journal | last1 = Viswambharan | first1 = H. | last2 = Ming | first2 = XF. | last3 = Zhu | first3 = S. | last4 = Hubsch | first4 = A. | last5 = Lerch | first5 = P. | last6 = Vergères | first6 = G. | last7 = Rusconi | first7 = S. | last8 = Yang | first8 = Z. | title = Reconstituted high-density lipoprotein inhibits thrombin-induced endothelial tissue factor expression through inhibition of RhoA and stimulation of phosphatidylinositol 3-kinase but not Akt/endothelial nitric oxide synthase. | journal = Circ Res | volume = 94 | issue = 7 | pages = 918-25 | month = Apr | year = 2004 | doi = 10.1161/01.RES.0000124302.20396.B7 | PMID = 14988229 }}</ref> | ||
====Anti-oxidant Funtions==== | ====Anti-oxidant Funtions==== | ||
The formation of free oxygen radicals contributes to the pathogenesis and progression of atherosclerotic plaques. Oxidized LDLs gets engulfed by macrophages, which leads to further oxidation and the production of foam cells. Oxidized LDLs acts as chemotactic agents for circulating monocytes, converts macrophages into foam cells, induce cytotoxic effects on the endothelium, inhibits motility of tissue macrophages, and stimulates the migration and proliferation of vascular smooth muscle cells.<ref name="pmid11795267">{{cite journal| author=Kita T, Kume N, Minami M, Hayashida K, Murayama T, Sano H et al.| title=Role of oxidized LDL in atherosclerosis. | journal=Ann N Y Acad Sci | year= 2001 | volume= 947 | issue= | pages= 199-205; discussion 205-6 | pmid=11795267 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11795267 }} </ref> HDL has been shown to inhibit the oxidative modification of oxidized LDLs,<ref name="pmid2344447">{{cite journal| author=Parthasarathy S, Barnett J, Fong LG| title=High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein. | journal=Biochim Biophys Acta | year= 1990 | volume= 1044 | issue= 2 | pages= 275-83 | pmid=2344447 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2344447 }} </ref> as well as preventing their infiltration into the vessel wall.<ref name="Galle-1994">{{Cite journal | last1 = Galle | first1 = J. | last2 = Ochslen | first2 = M. | last3 = Schollmeyer | first3 = P. | last4 = Wanner | first4 = C. | title = Oxidized lipoproteins inhibit endothelium-dependent vasodilation. Effects of pressure and high-density lipoprotein. | journal = Hypertension | volume = 23 | issue = 5 | pages = 556-64 | month = May | year = 1994 | doi = | PMID = 8175161 }}</ref> | The formation of free oxygen radicals contributes to the pathogenesis and progression of atherosclerotic plaques. Oxidized LDLs gets engulfed by macrophages, which leads to further oxidation and the production of foam cells. Oxidized LDLs acts as chemotactic agents for circulating monocytes, converts macrophages into foam cells, induce cytotoxic effects on the endothelium, inhibits motility of tissue macrophages, and stimulates the migration and proliferation of vascular smooth muscle cells.<ref name="pmid11795267">{{cite journal| author=Kita T, Kume N, Minami M, Hayashida K, Murayama T, Sano H et al.| title=Role of oxidized LDL in atherosclerosis. | journal=Ann N Y Acad Sci | year= 2001 | volume= 947 | issue= | pages= 199-205; discussion 205-6 | pmid=11795267 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11795267 }} </ref> HDL has been shown to inhibit the oxidative modification of oxidized LDLs,<ref name="pmid2344447">{{cite journal| author=Parthasarathy S, Barnett J, Fong LG| title=High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein. | journal=Biochim Biophys Acta | year= 1990 | volume= 1044 | issue= 2 | pages= 275-83 | pmid=2344447 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2344447 }} </ref> as well as preventing their infiltration into the vessel wall.<ref name="Galle-1994">{{Cite journal | last1 = Galle | first1 = J. | last2 = Ochslen | first2 = M. | last3 = Schollmeyer | first3 = P. | last4 = Wanner | first4 = C. | title = Oxidized lipoproteins inhibit endothelium-dependent vasodilation. Effects of pressure and high-density lipoprotein. | journal = Hypertension | volume = 23 | issue = 5 | pages = 556-64 | month = May | year = 1994 | doi = | PMID = 8175161 }}</ref> | ||
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====Anti-inflammatory Properties==== | ====Anti-inflammatory Properties==== | ||
HDL has anti-inflammatory functions in both endothelial cells and leukocytes. During inflammation, several leukocyte adhesion molecules are activated which promotes the binding of leukocytes and formation of atheroma. HDL has been shown to inhibit the activation of vascular cell adhesion molecule ([[VCAM-1]],<ref name="Dimayuga-1999">{{Cite journal | last1 = Dimayuga | first1 = P. | last2 = Zhu | first2 = J. | last3 = Oguchi | first3 = S. | last4 = Chyu | first4 = KY. | last5 = Xu | first5 = XO. | last6 = Yano | first6 = J. | last7 = Shah | first7 = PK. | last8 = Nilsson | first8 = J. | last9 = Cercek | first9 = B. | title = Reconstituted HDL containing human apolipoprotein A-1 reduces VCAM-1 expression and neointima formation following periadventitial cuff-induced carotid injury in apoE null mice. | journal = Biochem Biophys Res Commun | volume = 264 | issue = 2 | pages = 465-8 | month = Oct | year = 1999 | doi = 10.1006/bbrc.1999.1278 | PMID = 10529386 }}</ref> interleukin-1-induced expresion of [[E-selectin]],<ref name="Cockerill-2001">{{Cite journal | last1 = Cockerill | first1 = GW. | last2 = Huehns | first2 = TY. | last3 = Weerasinghe | first3 = A. | last4 = Stocker | first4 = C. | last5 = Lerch | first5 = PG. | last6 = Miller | first6 = NE. | last7 = Haskard | first7 = DO. | title = Elevation of plasma high-density lipoprotein concentration reduces interleukin-1-induced expression of E-selectin in an in vivo model of acute inflammation. | journal = Circulation | volume = 103 | issue = 1 | pages = 108-12 | month = Jan | year = 2001 | doi = | PMID = 11136694 }}</ref> interleukin-8, intracellular adhesion molecule (ICAM)-1, neutrophils,<ref name="Murphy-2011">{{Cite journal | last1 = Murphy | first1 = AJ. | last2 = Woollard | first2 = KJ. | last3 = Suhartoyo | first3 = A. | last4 = Stirzaker | first4 = RA. | last5 = Shaw | first5 = J. | last6 = Sviridov | first6 = D. | last7 = Chin-Dusting | first7 = JP. | title = Neutrophil activation is attenuated by high-density lipoprotein and apolipoprotein A-I in in vitro and in vivo models of inflammation. | journal = Arterioscler Thromb Vasc Biol | volume = 31 | issue = 6 | pages = 1333-41 | month = Jun | year = 2011 | doi = 10.1161/ATVBAHA.111.226258 | PMID = 21474825 }}</ref> monocytes,<ref name="Murphy-2008">{{Cite journal | last1 = Murphy | first1 = AJ. | last2 = Woollard | first2 = KJ. | last3 = Hoang | first3 = A. | last4 = Mukhamedova | first4 = N. | last5 = Stirzaker | first5 = RA. | last6 = McCormick | first6 = SP. | last7 = Remaley | first7 = AT. | last8 = Sviridov | first8 = D. | last9 = Chin-Dusting | first9 = J. | title = High-density lipoprotein reduces the human monocyte inflammatory response. | journal = Arterioscler Thromb Vasc Biol | volume = 28 | issue = 11 | pages = 2071-7 | month = Nov | year = 2008 | doi = 10.1161/ATVBAHA.108.168690 | PMID = 18617650 }}</ref> and also prevents the binding of T-lymphocytes to monocytes thereby preventing the formation of proinflammatory cytokines.<ref name="Carpintero-2010">{{Cite journal | last1 = Carpintero | first1 = R. | last2 = Gruaz | first2 = L. | last3 = Brandt | first3 = KJ. | last4 = Scanu | first4 = A. | last5 = Faille | first5 = D. | last6 = Combes | first6 = V. | last7 = Grau | first7 = GE. | last8 = Burger | first8 = D. | title = HDL interfere with the binding of T cell microparticles to human monocytes to inhibit pro-inflammatory cytokine production. | journal = PLoS One | volume = 5 | issue = 7 | pages = e11869 | month = | year = 2010 | doi = 10.1371/journal.pone.0011869 | PMID = 20686620 }}</ref> | HDL has anti-inflammatory functions in both endothelial cells and leukocytes. During inflammation, several leukocyte adhesion molecules are activated which promotes the binding of leukocytes and formation of atheroma. HDL has been shown to inhibit the activation of vascular cell adhesion molecule ([[VCAM-1]],<ref name="Dimayuga-1999">{{Cite journal | last1 = Dimayuga | first1 = P. | last2 = Zhu | first2 = J. | last3 = Oguchi | first3 = S. | last4 = Chyu | first4 = KY. | last5 = Xu | first5 = XO. | last6 = Yano | first6 = J. | last7 = Shah | first7 = PK. | last8 = Nilsson | first8 = J. | last9 = Cercek | first9 = B. | title = Reconstituted HDL containing human apolipoprotein A-1 reduces VCAM-1 expression and neointima formation following periadventitial cuff-induced carotid injury in apoE null mice. | journal = Biochem Biophys Res Commun | volume = 264 | issue = 2 | pages = 465-8 | month = Oct | year = 1999 | doi = 10.1006/bbrc.1999.1278 | PMID = 10529386 }}</ref> interleukin-1-induced expresion of [[E-selectin]],<ref name="Cockerill-2001">{{Cite journal | last1 = Cockerill | first1 = GW. | last2 = Huehns | first2 = TY. | last3 = Weerasinghe | first3 = A. | last4 = Stocker | first4 = C. | last5 = Lerch | first5 = PG. | last6 = Miller | first6 = NE. | last7 = Haskard | first7 = DO. | title = Elevation of plasma high-density lipoprotein concentration reduces interleukin-1-induced expression of E-selectin in an in vivo model of acute inflammation. | journal = Circulation | volume = 103 | issue = 1 | pages = 108-12 | month = Jan | year = 2001 | doi = | PMID = 11136694 }}</ref> interleukin-8, intracellular adhesion molecule (ICAM)-1, neutrophils,<ref name="Murphy-2011">{{Cite journal | last1 = Murphy | first1 = AJ. | last2 = Woollard | first2 = KJ. | last3 = Suhartoyo | first3 = A. | last4 = Stirzaker | first4 = RA. | last5 = Shaw | first5 = J. | last6 = Sviridov | first6 = D. | last7 = Chin-Dusting | first7 = JP. | title = Neutrophil activation is attenuated by high-density lipoprotein and apolipoprotein A-I in in vitro and in vivo models of inflammation. | journal = Arterioscler Thromb Vasc Biol | volume = 31 | issue = 6 | pages = 1333-41 | month = Jun | year = 2011 | doi = 10.1161/ATVBAHA.111.226258 | PMID = 21474825 }}</ref> monocytes,<ref name="Murphy-2008">{{Cite journal | last1 = Murphy | first1 = AJ. | last2 = Woollard | first2 = KJ. | last3 = Hoang | first3 = A. | last4 = Mukhamedova | first4 = N. | last5 = Stirzaker | first5 = RA. | last6 = McCormick | first6 = SP. | last7 = Remaley | first7 = AT. | last8 = Sviridov | first8 = D. | last9 = Chin-Dusting | first9 = J. | title = High-density lipoprotein reduces the human monocyte inflammatory response. | journal = Arterioscler Thromb Vasc Biol | volume = 28 | issue = 11 | pages = 2071-7 | month = Nov | year = 2008 | doi = 10.1161/ATVBAHA.108.168690 | PMID = 18617650 }}</ref> and also prevents the binding of T-lymphocytes to monocytes thereby preventing the formation of proinflammatory cytokines.<ref name="Carpintero-2010">{{Cite journal | last1 = Carpintero | first1 = R. | last2 = Gruaz | first2 = L. | last3 = Brandt | first3 = KJ. | last4 = Scanu | first4 = A. | last5 = Faille | first5 = D. | last6 = Combes | first6 = V. | last7 = Grau | first7 = GE. | last8 = Burger | first8 = D. | title = HDL interfere with the binding of T cell microparticles to human monocytes to inhibit pro-inflammatory cytokine production. | journal = PLoS One | volume = 5 | issue = 7 | pages = e11869 | month = | year = 2010 | doi = 10.1371/journal.pone.0011869 | PMID = 20686620 }}</ref> | ||
====Metabolic Functions==== | |||
In a study to determine the effects and mechanisms of HDL on glucose metabolism, 13 type 2 diabetic patients received intravenous reconstituted HDL. The result proved a reduction in the plasma glucose of the patients due to an increase in plasma insulin in addition to the activation of AMP-activated protein kinase in skeletal muscle. These findings suggest a role for HDL-raising therapies beyond atherosclerosis to address type 2 diabetes mellitus.<ref name="Drew-2009">{{Cite journal | last1 = Drew | first1 = BG. | last2 = Duffy | first2 = SJ. | last3 = Formosa | first3 = MF. | last4 = Natoli | first4 = AK. | last5 = Henstridge | first5 = DC. | last6 = Penfold | first6 = SA. | last7 = Thomas | first7 = WG. | last8 = Mukhamedova | first8 = N. | last9 = de Courten | first9 = B. | title = High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus. | journal = Circulation | volume = 119 | issue = 15 | pages = 2103-11 | month = Apr | year = 2009 | doi = 10.1161/CIRCULATIONAHA.108.843219 | PMID = 19349317 }}</ref> | |||
====Anti-apoptotic Functions==== | ====Anti-apoptotic Functions==== | ||
====Vasodilatory Functions==== | ====Vasodilatory Functions==== | ||
==References== | ==References== | ||
Revision as of 21:26, 13 September 2013
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayokunle Olubaniyi, M.B,B.S [2]
Overview
Physiology
HDL Metabolism
The metabolism of HDL can also be described as the Reverse Cholesterol Transport System. HDL serves a mode of transportation for the excess cholesterol from peripheral tissues to the liver.
Synthesis and Uptake of Cholesterol
- HDL consists majorly of apo A-I and/or apo A-II. Both organs synthesize apo A-I while only the liver synthesizes apo A-II. HDL is normally synthesized consisting of composed mainly of phospholipids and apolipoproteins.
- Free apo A-I is released into the plasma as nascent HDL. This readily takes up excess free cholesterol (FC) from peripheral tissues such as fibroblasts and macrophages and arterial wall mediated by either ATP-binding cassette A1 (ABCA1), G1/G4, scavenger receptor class B type 1 (SR-B1), Cyp27A1, caveloin, and passive diffusion, leading to the formation of discoid HDL (a.k.a. pre-βHDL).
- Apo A-I activates lecithin:cholesteryl acetyltransferase (LCAT) which catalyses the esterification of the free cholesterol bound to the discoid HDL. The Apolipoprotein A1 acts as a signal protein in mobilizing cholesterol esters from within the cells.
aaaaavvvvvvccccccattttttttttttttttttttttttaaaaaaaaaaLCAT
aaaaavvvvvvaaaaaaaaaaaLecithin + Cholesterol ———-> Lysolecithin + Cholesterol ester
Maturation and Transfer of Cholesterol
- The esterified cholesterol moves into the hydrophobic core of the HDL, changing the HDL particle from discoid to spherical (mature HDL). This process also prevents the re-uptake of cholesterol by cells. LCAT is responsible for the maturation of HDL particle.
- The esterified cholesterol can be delivered back to the liver through a number of routes:
- By the action of cholesterylester transfer protein (CETP) - CETP, secreted in the liver, transfers cholesterol from HDL to the apo B–containing lipoproteins e.g., very low-density lipoprotein (VLDL) or intermediate-density lipoprotein (IDL) to be taken up by the liver. Mutations of this transport protein gene causes familial HDL deficiencies and Tangier disease
- HDL particles may be taken up directly by the liver
- Free cholesterol may be taken up directly by the liver
- HDL cholesterol esters may be selectively taken up via the scavenger receptor SR-B1, which is expressed in the liver.
Catabolism
- Triglyceride lipases degrade these cholesterol-deplete HDL particles into small, dense HDL which after dissociation, release apo A-I (nascent HDL). The apo A-1 then either rapidly reuptakes cholesterol again by ABCA1 to form discoid HDL or it is endocytosed in the kidney tubule or cleared via glomerular filtration.
Functions
Atheroprotection
HDL and apo A-I mediate the reverse cholesterol transport from atherosclerotic plaques.
Anti-coagulant Funtions
HDL has the ability to inhibit platelet activation and aggregation by directly inhibiting platelet activation,[1][2] downregulates thromboxane A2 synthesis,[3] increases the synthesis of prostacyclin,[4] and lowers the expression of tissue factor which is required in the coagulation process.[5]
Anti-oxidant Funtions
The formation of free oxygen radicals contributes to the pathogenesis and progression of atherosclerotic plaques. Oxidized LDLs gets engulfed by macrophages, which leads to further oxidation and the production of foam cells. Oxidized LDLs acts as chemotactic agents for circulating monocytes, converts macrophages into foam cells, induce cytotoxic effects on the endothelium, inhibits motility of tissue macrophages, and stimulates the migration and proliferation of vascular smooth muscle cells.[6] HDL has been shown to inhibit the oxidative modification of oxidized LDLs,[7] as well as preventing their infiltration into the vessel wall.[8]
Anti-inflammatory Properties
HDL has anti-inflammatory functions in both endothelial cells and leukocytes. During inflammation, several leukocyte adhesion molecules are activated which promotes the binding of leukocytes and formation of atheroma. HDL has been shown to inhibit the activation of vascular cell adhesion molecule (VCAM-1,[9] interleukin-1-induced expresion of E-selectin,[10] interleukin-8, intracellular adhesion molecule (ICAM)-1, neutrophils,[11] monocytes,[12] and also prevents the binding of T-lymphocytes to monocytes thereby preventing the formation of proinflammatory cytokines.[13]
Metabolic Functions
In a study to determine the effects and mechanisms of HDL on glucose metabolism, 13 type 2 diabetic patients received intravenous reconstituted HDL. The result proved a reduction in the plasma glucose of the patients due to an increase in plasma insulin in addition to the activation of AMP-activated protein kinase in skeletal muscle. These findings suggest a role for HDL-raising therapies beyond atherosclerosis to address type 2 diabetes mellitus.[14]
Anti-apoptotic Functions
Vasodilatory Functions
References
- ↑ Calkin, AC.; Drew, BG.; Ono, A.; Duffy, SJ.; Gordon, MV.; Schoenwaelder, SM.; Sviridov, D.; Cooper, ME.; Kingwell, BA. (2009). "Reconstituted high-density lipoprotein attenuates platelet function in individuals with type 2 diabetes mellitus by promoting cholesterol efflux". Circulation. 120 (21): 2095–104. doi:10.1161/CIRCULATIONAHA.109.870709. PMID 19901191. Unknown parameter
|month=ignored (help) - ↑ Lerch, PG.; Spycher, MO.; Doran, JE. (1998). "Reconstituted high density lipoprotein (rHDL) modulates platelet activity in vitro and ex vivo". Thromb Haemost. 80 (2): 316–20. PMID 9716159. Unknown parameter
|month=ignored (help) - ↑ Brill, A.; Fuchs, TA.; Chauhan, AK.; Yang, JJ.; De Meyer, SF.; Köllnberger, M.; Wakefield, TW.; Lämmle, B.; Massberg, S. (2011). "von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models". Blood. 117 (4): 1400–7. doi:10.1182/blood-2010-05-287623. PMID 20959603. Unknown parameter
|month=ignored (help) - ↑ Fleisher, LN.; Tall, AR.; Witte, LD.; Miller, RW.; Cannon, PJ. (1982). "Stimulation of arterial endothelial cell prostacyclin synthesis by high density lipoproteins". J Biol Chem. 257 (12): 6653–5. PMID 7045092. Unknown parameter
|month=ignored (help) - ↑ Viswambharan, H.; Ming, XF.; Zhu, S.; Hubsch, A.; Lerch, P.; Vergères, G.; Rusconi, S.; Yang, Z. (2004). "Reconstituted high-density lipoprotein inhibits thrombin-induced endothelial tissue factor expression through inhibition of RhoA and stimulation of phosphatidylinositol 3-kinase but not Akt/endothelial nitric oxide synthase". Circ Res. 94 (7): 918–25. doi:10.1161/01.RES.0000124302.20396.B7. PMID 14988229. Unknown parameter
|month=ignored (help) - ↑ Kita T, Kume N, Minami M, Hayashida K, Murayama T, Sano H; et al. (2001). "Role of oxidized LDL in atherosclerosis". Ann N Y Acad Sci. 947: 199–205, discussion 205-6. PMID 11795267.
- ↑ Parthasarathy S, Barnett J, Fong LG (1990). "High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein". Biochim Biophys Acta. 1044 (2): 275–83. PMID 2344447.
- ↑ Galle, J.; Ochslen, M.; Schollmeyer, P.; Wanner, C. (1994). "Oxidized lipoproteins inhibit endothelium-dependent vasodilation. Effects of pressure and high-density lipoprotein". Hypertension. 23 (5): 556–64. PMID 8175161. Unknown parameter
|month=ignored (help) - ↑ Dimayuga, P.; Zhu, J.; Oguchi, S.; Chyu, KY.; Xu, XO.; Yano, J.; Shah, PK.; Nilsson, J.; Cercek, B. (1999). "Reconstituted HDL containing human apolipoprotein A-1 reduces VCAM-1 expression and neointima formation following periadventitial cuff-induced carotid injury in apoE null mice". Biochem Biophys Res Commun. 264 (2): 465–8. doi:10.1006/bbrc.1999.1278. PMID 10529386. Unknown parameter
|month=ignored (help) - ↑ Cockerill, GW.; Huehns, TY.; Weerasinghe, A.; Stocker, C.; Lerch, PG.; Miller, NE.; Haskard, DO. (2001). "Elevation of plasma high-density lipoprotein concentration reduces interleukin-1-induced expression of E-selectin in an in vivo model of acute inflammation". Circulation. 103 (1): 108–12. PMID 11136694. Unknown parameter
|month=ignored (help) - ↑ Murphy, AJ.; Woollard, KJ.; Suhartoyo, A.; Stirzaker, RA.; Shaw, J.; Sviridov, D.; Chin-Dusting, JP. (2011). "Neutrophil activation is attenuated by high-density lipoprotein and apolipoprotein A-I in in vitro and in vivo models of inflammation". Arterioscler Thromb Vasc Biol. 31 (6): 1333–41. doi:10.1161/ATVBAHA.111.226258. PMID 21474825. Unknown parameter
|month=ignored (help) - ↑ Murphy, AJ.; Woollard, KJ.; Hoang, A.; Mukhamedova, N.; Stirzaker, RA.; McCormick, SP.; Remaley, AT.; Sviridov, D.; Chin-Dusting, J. (2008). "High-density lipoprotein reduces the human monocyte inflammatory response". Arterioscler Thromb Vasc Biol. 28 (11): 2071–7. doi:10.1161/ATVBAHA.108.168690. PMID 18617650. Unknown parameter
|month=ignored (help) - ↑ Carpintero, R.; Gruaz, L.; Brandt, KJ.; Scanu, A.; Faille, D.; Combes, V.; Grau, GE.; Burger, D. (2010). "HDL interfere with the binding of T cell microparticles to human monocytes to inhibit pro-inflammatory cytokine production". PLoS One. 5 (7): e11869. doi:10.1371/journal.pone.0011869. PMID 20686620.
- ↑ Drew, BG.; Duffy, SJ.; Formosa, MF.; Natoli, AK.; Henstridge, DC.; Penfold, SA.; Thomas, WG.; Mukhamedova, N.; de Courten, B. (2009). "High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus". Circulation. 119 (15): 2103–11. doi:10.1161/CIRCULATIONAHA.108.843219. PMID 19349317. Unknown parameter
|month=ignored (help)