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High density lipoprotein classification
Introduction
Overview
Overview
High-density lipoprotein (HDL) does not represent one structure but rather a series of lipoproteins that are sequentially produced. HDL dynamically switches between different conformations. Fractionated HDL particles can be classified based on physiochemical properties, cholesterol component, apolipoprotein composition, electrophoretic mobility, density, and biological function.[1][2] HDL concentration in the serum can be classified into either low and high when the serum HDL concentration ā„ 60mg/dL and < 40 mg/dL, respectively.[3]
Classification
Classification
Classification by Concentration
High HDL
High HDL level is defined by the National Cholesterol Education Program (NCEP) as serum HDL concentration ā„ 60mg/dL.[3]
Low HDL
Low HDL level is defined by the National Cholesterol Education Program (NCEP) as serum HDL concentration < 40 mg/dL.[3]
Classification by Structural and Functional Characteristics
HDLs are highly heterogenous in their physiochemical characteristics due to the differences in relative composition of intercalated apolipoproteins thus may be separated based upon buoyant density, size, charge, or apolipoprotein composition. Moreover, the amphiphatic helical structure of apoA-I possesses a hinge domain that allows it to switch between different conformations corresponding to HDLs of variable size.[4] With density gradient ultracentrifugation, HDLs can be separated into HDL2, HDL3, and very-high-density lipoprotein (VHDL). Nondenaturing polyacrylamide gradient gel electrophoresis may also be used to fractionate HDLs into five distinct populations of descending size: HDL2b, HDL2a, HDL3a, HDL3b, and HDL3c.[5][6] Isopycnic density gradient ultracentrifugation has been used to analyze the fasting plasma to yield equivalent delineations as well.[7][8] Yet another method of classifying HDL lipoprotein particles by size is nuclear magnetic resonance (NMR).[9] Two-dimensional gel electrophoresis technique can be used to resolve HDL particles in the plasma into lipid-poor pre-β-HDLs and α-HDL that predominantly contains mature spherical cholesteryl esters.[10]
Density
HDLs may be ultracentrifugally fractionated into two major populations.[11][12][13]
| Type | Size | Density |
| HDL2 | 1.063-1.125 g/ml | 8.8 to 13 nm |
| HDL3 | 1.125-1.21 g/ml | 7.3 to 8.2 nm |
Size
HDL may be isolated on the basis of size by non-denaturing polyacrylamide gradient gel electrophoresis or by isopycnic density gradient ultracentrifugation.[11]
In the order of decreasing size:[13]
- HDL2b
- HDL2a
- HDL3a
- HDL3b
- HDL3c
Another classification is:
- Very large HDL particles (VL-HDL)
- Large HDL particles (L-HDL)
- Medium HDL particles (M-HDL)
- Small HDL particles (S-HDL)
- Very-small HDL particles (VS-HDL)
- Pre-β-1 HDL (role in macrophage cholesterol efflux)[1]
Apolipoprotein Content
High density lipoproteins can be immunoseparated on the basis of apolipoprotein composition into particles containing different apolipoproteins. The two major apolipoproteins found within HDL particles are the apoA-I and apoA-II.[14][15] Several other minor apolipoproteins associated with HDL include apoA-IV, apoA-V, apoC-I, apoC-II, apoC-III, and apoE.[16] However, LpA-I and LpA-I:LpA-II constitute the major portions of ciculating HDLs.
Surface Charge
HDL can be separated according to charge by agarose gel electrophoresis.[11]
Note that pre-beta < pre-alpha < alpha.
- Pre-beta (positive)
- Pre-alpha
- Alpha (negative)
References
References
- ā 1.0 1.1 Rosenson RS, Brewer HB, Chapman MJ, Fazio S, Hussain MM, Kontush A; et al. (2011). “HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events”. Clin Chem. 57 (3): 392ā410. doi:10.1373/clinchem.2010.155333. PMIDĀ 21266551.
- ā Rosenson RS, Brewer HB, Ansell B, Barter P, Chapman MJ, Heinecke JW; et al. (2013). “Translation of High-Density Lipoprotein Function Into Clinical Practice: Current Prospects and Future Challenges”. Circulation. 128 (11): 1256ā1267. doi:10.1161/CIRCULATIONAHA.113.000962. PMIDĀ 24019446.
- ā 3.0 3.1 3.2 National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002). “Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report”. Circulation. 106 (25): 3143ā421. PMIDĀ 12485966.
- ā Reschly, EJ.; Sorci-Thomas, MG.; Davidson, WS.; Meredith, SC.; Reardon, CA.; Getz, GS. (2002). “Apolipoprotein A-I alpha -helices 7 and 8 modulate high density lipoprotein subclass distribution”. J Biol Chem. 277 (12): 9645ā54. doi:10.1074/jbc.M107883200. PMIDĀ 11744719. Unknown parameter
|month=ignored (help) - ā Blanche, PJ.; Gong, EL.; Forte, TM.; Nichols, AV. (1981). “Characterization of human high-density lipoproteins by gradient gel electrophoresis”. Biochim Biophys Acta. 665 (3): 408ā19. PMIDĀ 7295744. Unknown parameter
|month=ignored (help) - ā Anderson, DW.; Nichols, AV.; Forte, TM.; Lindgren, FT. (1977). “Particle distribution of human serum high density lipoproteins”. Biochim Biophys Acta. 493 (1): 55ā68. PMIDĀ 195628. Unknown parameter
|month=ignored (help) - ā Goulinet, S.; Chapman, MJ. (1997). “Plasma LDL and HDL subspecies are heterogenous in particle content of tocopherols and oxygenated and hydrocarbon carotenoids. Relevance to oxidative resistance and atherogenesis”. Arterioscler Thromb Vasc Biol. 17 (4): 786ā96. PMIDĀ 9108795. Unknown parameter
|month=ignored (help) - ā Tall, AR.; Blum, CB.; Forester, GP.; Nelson, CA. (1982). “Changes in the distribution and composition of plasma high density lipoproteins after ingestion of fat”. J Biol Chem. 257 (1): 198ā207. PMIDĀ 6796585. Unknown parameter
|month=ignored (help) - ā Rifai, Nader.; Warnick, G. Russell.; Dominiczak, Marek H. (2000). Handbook of lipoprotein testin. Washington, DC: AACC Press. ISBNĀ 1-890883-35-2.
- ā Asztalos, BF.; Schaefer, EJ. (2003). “High-density lipoprotein subpopulations in pathologic conditions”. Am J Cardiol. 91 (7A): 12Eā17E. PMIDĀ 12679198. Unknown parameter
|month=ignored (help) - ā 11.0 11.1 11.2 11.3 Krimbou L, Tremblay M, Davignon J, Cohn JS (1997). “Characterization of human plasma apolipoprotein E-containing lipoproteins in the high density lipoprotein size range: focus on pre-beta1-LpE, pre-beta2-LpE, and alpha-LpE”. J Lipid Res. 38 (1): 35ā48. PMIDĀ 9034198.
- ā Chapman MJ, Goldstein S, Lagrange D, Laplaud PM (1981). “A density gradient ultracentrifugal procedure for the isolation of the major lipoprotein classes from human serum”. J Lipid Res. 22 (2): 339ā58. PMIDĀ 6787159.
- ā 13.0 13.1 13.2 Rye KA, Barter PJ (2012). “Predictive value of different HDL particles for the protection against or risk of coronary heart disease”. Biochim Biophys Acta. 1821 (3): 473ā80. doi:10.1016/j.bbalip.2011.10.012. PMIDĀ 22051746.
- ā Brewer, HB.; Lux, SE.; Ronan, R.; John, KM. (1972). “Amino acid sequence of human apoLp-Gln-II (apoA-II), an apolipoprotein isolated from the high-density lipoprotein complex”. Proc Natl Acad Sci U S A. 69 (5): 1304ā8. PMIDĀ 4338591. Unknown parameter
|month=ignored (help) - ā Brewer, HB.; Fairwell, T.; LaRue, A.; Ronan, R.; Houser, A.; Bronzert, TJ. (1978). “The amino acid sequence of human APOA-I, an apolipoprotein isolated from high density lipoproteins”. Biochem Biophys Res Commun. 80 (3): 623ā30. PMIDĀ 204308. Unknown parameter
|month=ignored (help) - ā Alaupovic, P. (1996). “Significance of apolipoproteins for structure, function, and classification of plasma lipoproteins”. Methods Enzymol. 263: 32ā60. PMIDĀ 8748999.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]
