High density lipoprotein physiology: Difference between revisions
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====Anti-inflammatory Properties==== | ====Anti-inflammatory Properties==== | ||
During inflammation, several leukocyte adhesion molecules are activated which promotes the binding of leukocytes and formation of atheroma. HDL has been shown to inhibit 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, and expression of monocyte chemotactic protein (MCP)-1. | 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 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, and expression of monocyte chemotactic protein (MCP)-1. | ||
====Anti-apoptotic Functions==== | ====Anti-apoptotic Functions==== | ||
====Vasodilatory Functions==== | ====Vasodilatory Functions==== | ||
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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
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.[1] HDL has been shown to inhibit the oxidative modification of oxidized LDLs,[2] as well as preventing their infiltration into the vessel wall.[3]
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 vascular cell adhesion molecule (VCAM-1,[4] interleukin-1-induced expresion of E-selectin,[5] interleukin-8, intracellular adhesion molecule (ICAM)-1, and expression of monocyte chemotactic protein (MCP)-1.
Anti-apoptotic Functions
Vasodilatory Functions
Metabolic Functions
References
- ↑ 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)