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Biomechanics and Modeling in Mechanobiology

, Volume 13, Issue 2, pp 313–326 | Cite as

Flow-dependent concentration polarization and the endothelial glycocalyx layer: multi-scale aspects of arterial mass transport and their implications for atherosclerosis

  • P. E. Vincent
  • P. D. Weinberg
Original Paper

Abstract

Atherosclerosis is the underlying cause of most heart attacks and strokes. It is thereby the leading cause of death in the Western world, and it places a significant financial burden on health care systems. There is evidence that complex, multi-scale arterial mass transport processes play a key role in the development of atherosclerosis. Such processes can be controlled both by blood flow patterns and by properties of the arterial wall. This short review focuses on one vascular-scale, flow-regulated arterial mass transport process, namely concentration polarization of low density lipoprotein at the luminal surface of the arterial endothelium, and on one cellular-scale, structural determinant of arterial wall mass transport, namely the endothelial glycocalyx layer. Both have attracted significant attention in recent years. In addition to reviewing and appraising relevant literature, we propose various directions for future work.

Keywords

Atherosclerosis Mass transport Endothelial glycocalyx layer Concentration polarization Low density lipoprotein 

Notes

Acknowledgments

The authors are grateful to the British Heart Foundation (BHF) and the BHF Centre of Research Excellence at Imperial College London for funding studies of arterial mass transport and its modulation by the EGL. The authors would also like to thank Fernando Bresme and Amparo Galindo for useful discussions regarding molecular-scale modeling of the EGL.

References

  1. Adams CMW (1973) Tissue changes and lipid entry in developing atheroma. In: Porter R, Knight J (eds) Ciba foundation symposium 12-atherogenesis: initiating factors, Novartis Foundation Symposia. Wiley, ChichesterGoogle Scholar
  2. Adamson RH, Clough G (1992) Plasma proteins modify the endothelial cell glycocalyx of frog mesenteric microvessels. J Physiol 445:473Google Scholar
  3. Adamson RH, Lenz JF, Zhang X, Adamson GN, Weinbaum S, Curry FE (2004) Oncotic pressures opposing filtration across non-fenestrated rat microvessels. J Physiol 557:889Google Scholar
  4. Adamson RH, Sarai RK, Altangerel A, Clark JF, Weinbaum S, Curry FE (2013) Microvascular permeability to water is independent of shear stress, but dependent on flow direction. Am J Physiol Heart Circ Physiol 304:H1077Google Scholar
  5. Albelda SM, Sampson PM, Haselton FR, McNiff JM, Mueller SN, Williams SK, Fishman AP, Levine EM (1988) Permeability characteristics of cultured endothelial cell monolayers. J Appl Physiol 64:308Google Scholar
  6. Annecke T, Fischer J, Hartmann H, Tschoep J, Rehm M, Conzen P, Sommerhoff CP, Becker BF (2011) Shedding of the coronary endothelial glycocalyx: effects of hypoxia/reoxygenation vs ischaemia/reperfusion. Brit J Anaesth 107:679Google Scholar
  7. Atmeh RF (1990) Isolation and identification of HDL particles of low molecular weight. J Lipid Res 31:1771Google Scholar
  8. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, Watson AD, Lusis AJ (1995) Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 91:2488Google Scholar
  9. Bratzler RL, Chisolm GM, Colton CK, Smith KA, Lees RS (1977) The distribution of labeled low-density lipoproteins across the rabbit thoracic aorta in vivo. Atherosclerosis 28:289Google Scholar
  10. Caro CG, Fitz-Gerald JM, Schroter RC (1969) Arterial wall shear and distribution of early atheroma in man. Nature 223:1159Google Scholar
  11. Caro CG, Fitz-Gerald JM, Schroter RC (1971) Atheroma and arterial wall shear. Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis. Proc R Soc Lond B Biol Sci 177:109Google Scholar
  12. Chang YS, Munn LL, Hillsley MV, Dull RO, Yuan J, Lakshminarayanan S, Gardner TW, Jain RK, Tarbell JM (2000) Effect of vascular endothelial growth factor on cultured endothelial cell monolayer transport properties. Microvasc Res 59:265Google Scholar
  13. Chen B, Fu BM (2004) An electrodiffusion-filtration model for effects of endothelial surface glycocalyx on microvessel permeability to macromolecules. J Biomech Eng 126:614Google Scholar
  14. Chen X, Jaron D, Barbee KA, Buerk DG (2006) The influence of radial RBC distribution, blood velocity profiles, and glycocalyx on coupled NO/O\(_2\) transport. J Appl Physiol 100:482Google Scholar
  15. Cheng C, de Crom R, van Haperen R, Helderman F, Mousavi GB, van Damme LCA, Kirschbaum SW, Slager CJ, van der Steen AFW, Krams R (2004) The role of shear stress in atherosclerosis: action through gene expression and inflammation. Cell Biochem Biophys 41:279Google Scholar
  16. Choi HW, Ferrara KW, Barakat AI (2007) Modulation of ATP/ADP concentration at the endothelial surface by shear stress: effect of flow recirculation. Ann Biomed Eng 35:505Google Scholar
  17. Choi HW, Barakat AI (2009) Modulation of ATP/ADP concentration at the endothelial cell surface by flow: effect of cell topography. Ann Biomed Eng 37:2459Google Scholar
  18. Curry FE, Adamson RH (2012) Endothelial glycocalyx: permeability barrier and mechanosensor. Ann Biomed Eng 40:828Google Scholar
  19. Curry FE, Michel CC (1980) A fiber matrix model of capillary permeability. Microvasc Res 20:96Google Scholar
  20. Dabagh M, Jalali P, Tarbell JM (2009) The transport of LDL across the deformable arterial wall: the effect of endothelial cell turnover and intimal deformation under hypertension. Am J Physiol Heart Circ Physiol 297:H983Google Scholar
  21. Damiano ER, Long DS, Smith ML (2004) Estimation of viscosity profiles using velocimetry data from parallel flows of linearly viscous fluids: application to microvascular haemodynamics. J Fluid Mech 512:1zbMATHGoogle Scholar
  22. Danova-Okpetu D (2005) Macromolecular studies of the dynamic structure and mechanical properties of the endothelial surface layer, PhD thesis. Johns HopkinsGoogle Scholar
  23. Deng X, Marois Y, How T, Merhi Y, King M, Guidoin R, Karino T (1995) Luminal surface concentration of lipoprotein (LDL) and its effect on the wall uptake of cholesterol by canine carotid arteries. J Vasc Surg 21:135Google Scholar
  24. Ding Z, Fan Y, Deng X (2009) Effect of LDL concentration polarization on the uptake of LDL by human endothelial cells and smooth muscle cells co-cultured. Acta Bioch Bioph Sin 41:146Google Scholar
  25. Dull RO, Jo H, Sill H, Hollis TM, Tarbell JM (1991) The effect of varying albumin concentration and hydrostatic pressure on hydraulic conductivity and albumin permeability of cultured endothelial monolayers. Microvasc Res 41:390Google Scholar
  26. Ebong EE, Macaluso FP, Spray DC, Tarbell JM (2011) Imaging the endothelial glycocalyx in vitro by rapid freezing/freeze substitution transmission electron microscopy. Arterioscl Throm Vas 31:1908Google Scholar
  27. Ethier CR (2002) Computational modeling of mass transfer and links to atherosclerosis. Ann Biomed Eng 30:461Google Scholar
  28. Faergeman O (2003) Coronary artery disease—genes, drugs and the agricultural connection. Elsevier, AmsterdamGoogle Scholar
  29. Fatouraee N, Deng X, Champlain A, Guidoin R (1998) Concentration polarization of low density lipoproteins (LDL) in the arterial system. Ann NY Acad Sci 858:137Google Scholar
  30. Flores SC, Bernauer J, Shin S, Zhou R, Huang X (2012) Multiscale modeling of macromolecular biosystems. Brief Bioinform 13:395Google Scholar
  31. Fry DL (1968) Acute vascular endothelial changes associated with increased blood velocity gradients. Circ Res 22:165Google Scholar
  32. Fu BM, Weinbaum S, Tsay RY, Curry FE (1994) A junction-orifice-fiber entrance layer model for capillary permeability: application to frog mesenteric capillaries. J Biomech Eng 116:502Google Scholar
  33. Fu BM, Chen B, Chen W (2003) An electrodiffusion model for effects of surface glycocalyx layer on microvessel permeability. Am J Phys Heart Circ Physiol 284:H1240Google Scholar
  34. Gao L, Lipowsky HH (2009) Measurement of solute transport in the endothelial glycocalyx using indicator dilution techniques. Ann Biomed Eng 37:1781Google Scholar
  35. Gao L, Lipowsky HH (2010) Composition of the endothelial glycocalyx and its relation to its thickness and diffusion of small solutes. Microvasc Res 80:394Google Scholar
  36. Gniewek P, Kolinski A (2012) Coarse-grained modeling of mucus barrier properties. Biophys J 102:195Google Scholar
  37. Gorog P, Born GV (1982) Increased uptake of circulating low-density lipoproteins and fibrinogen by arterial walls after removal of sialic acids from their endothelial surface. Br J Exp Pathol 63:447Google Scholar
  38. Hahn C, Schwartz MA (2009) Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol 10:53Google Scholar
  39. Henry CBS, Duling BR (1999) Permeation of the luminal capillary glycocalyx is determined by hyaluronan. Am J Physiol Heart Circ Physiol 277:H508Google Scholar
  40. Henry CB, Duling BR (2000) TNF-\({\alpha }\) increases entry of macromolecules into luminal endothelial cell glycocalyx. Am J Physiol Heart Circ Physiol 279:H2815Google Scholar
  41. Hu X, Weinbaum S (1999) A new view of Starling’s hypothesis at the microstructural level. Microvasc Res 58:281Google Scholar
  42. Hu X, Adamson RH, Liu B, Curry FE, Weinbaum S (2000) Starling forces that oppose filtration after tissue oncotic pressure is increased. Am J Physiol Heart Circ Physiol 279:1724Google Scholar
  43. Jellinek H (1983) The drainage of transmural flow and the consequences of its insufficiency. In: Schettler G, Nerem RM, Schmid-Schonbein H, Morl H, Diehm C (eds) Fluid dynamics as a localizing factor for atherosclerosis. Springer, BerlinGoogle Scholar
  44. John K, Barakat AI (2001) Modulation of ATP/ADP concentration at the endothelial surface by shear stress: effect of flow-induced ATP release. Ann Biomed Eng 29:740Google Scholar
  45. Koo A, Dewey CF, García-Cardeña G (2013) Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells. Am J Physiol Cell Physiol 304:C137Google Scholar
  46. Ku DN, Giddens DP, Zarins CK, Glagov S (1985) Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis 5:293Google Scholar
  47. Lantz J, Karlsson M (2012) Large eddy simulation of LDL surface concentration in a subject specific human aorta. J Biomech 45:537Google Scholar
  48. Lervik A, Bresme F, Kjelstrup S (2013) Molecular dynamics simulations of the Ca\(^{2+}\) pump: a structural analysis. Phys Chem Chem Phys 14:3543Google Scholar
  49. Levick JR, Michel CC (1973) The effect of bovine albumin on the Permeability of frog mesenteric capillaries. Exp Physiol 58:87Google Scholar
  50. Lipowsky HH, Lescanic A (2013) Shear-dependent adhesion of leukocytes and lectins to the endothelium and concurrent changes in thickness of the glycocalyx of post-capillary venules in the low-flow state. Microcirculation 20:149Google Scholar
  51. Liu X, Pu F, Fan Y, Deng X, Li D, Li S (2009) A numerical study on the flow of blood and the transport of LDL in the human aorta: the physiological significance of the helical flow in the aortic arch. Am J Physiol-Heart C 297:H163Google Scholar
  52. Liu X, Fan Y, Deng X (2011) Effect of the endothelial glycocalyx layer on arterial LDL transport under normal and high pressure. J Theor Biol 283:71Google Scholar
  53. Luckett PM, Fischbarg J, Bhattacharya J, Silverstein SC (1989) Hydraulic conductivity of endothelial cell monolayers cultured on human amnion. Am J Physiol 256:H1675Google Scholar
  54. Mackay J, Mensah G (2004) The atlas of heart disease and stroke. World Health Organization, GenevaGoogle Scholar
  55. Mason J, Curry F, Michel C (1977) The effects of proteins upon the filtration coefficient of individually perfused frog mesenteric capillaries. Microvasc Res 13:185Google Scholar
  56. Megens RTA, Reitsma S, Schiffers PHM, Hilgers RHP, De Mey JGR, Slaaf DW, oude Egbrink MGA, van Zandvoort MAMJ (2007) Two-photon microscopy of vital murine elastic and muscular arteries. Combined structural and functional imaging with subcellular resolution. J Vasc Res 44:87Google Scholar
  57. Meng W, Yu F, Chen H, Zhang J, Zhang E, Dian K, Shi Y (2009) Concentration polarization of high-density lipoprotein and its relation with shear stress in an in vitro model. J Biomed Biotechnol 2009: 695838Google Scholar
  58. Michel CC (1980) Filtration coefficients and osmotic reflexion coefficients of the walls of single frog mesenteric capillaries. J Physiol 309:341Google Scholar
  59. Michel CC, Phillips ME, Turner MR (1985) The effects of native and modified bovine serum albumin on the permeability of frog mesenteric capillaries. J Physiol 360:333Google Scholar
  60. Michel CC (1997) Starling: the formulation of his hypothesis of microvascular fluid exchange and its significance after 100 years. Exp Physiol 82:1Google Scholar
  61. Napoli C, de Nigris F, Williams-Ignarro S, Pignalosa O, Sica V, Ignarro LJ (2006) Nitric oxide and atherosclerosis: an update. Nitric Oxide-Biol Ch 15:265Google Scholar
  62. Pang Z, Tarbell JM (2003) In vitro study of Starling’s hypothesis in a cultured monolayer of bovine aortic endothelial cells. J Vasc Res 40:351Google Scholar
  63. Pries AR, Secomb TW, Gaehtgens P (2000) The endothelial surface layer. Pflugers Arch 440:653Google Scholar
  64. Rader DJ (2003) Regulation of reverse cholesterol transport and clinical implications. Am J Cardiol 92:42Google Scholar
  65. Reitsma S, Slaaf DW, Vink H, van Zandvoort MAMJ, Oude Egbrink MGA (2007) The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch 454:345Google Scholar
  66. Rindfleisch E (1872) A manual of pathological histology to serve as an introduction to the study of mordib anatomy. The New Sydenham Society, LondonGoogle Scholar
  67. Scharfstein H, Gutstein WH, Lewis L (1963) Changes of boundary layer flow in model systems: implications for initiation of endothelial injury. Circ Res 13:580Google Scholar
  68. Schnitzer JE, Carley WW, Palade GE (1988) Albumin interacts specifically with a 60-kDa microvascular endothelial glycoprotein. PNAS 85:6773Google Scholar
  69. Schnitzer JE, Carley WW, Palade GE (1988) Specific albumin binding to microvascular endothelium in culture. Am J Physiol 254:H425Google Scholar
  70. Schwartz CJ, Valente AJ, Sprague EA (1993) A modern view of atherogenesis. Am J Cardiol 71:9BGoogle Scholar
  71. Secomb TW, Hsu R, Pries AR (2001) Motion of red blood cells in a capillary with an endothelial surface layer: effect of flow velocity. Am J Physiol Heart Circ Physiol 281:H629Google Scholar
  72. Shaaban AM, Duerinckx AJ (2000) Wall shear stress and early atherosclerosis: a review. Am J Roentgenol 174:1657Google Scholar
  73. Smith ML, Long DS, Damiano ER, Ley K (2003) Near-wall micro-PIV reveals a hydrodynamically relevant endothelial surface layer in venules in vivo. Biophys J 85:637Google Scholar
  74. Stace TM, Damiano ER (2001) An electrochemical model of the transport of charged molecules through the capillary glycocalyx. Biophys J 80:1670Google Scholar
  75. Stevens AP, Hlady V, Dull RO (2007) Fluorescence correlation spectroscopy can probe albumin dynamics inside lung endothelial glycocalyx. Am J Physiol Lung Cell Mol Physiol 293:L328Google Scholar
  76. Suttorp N, Hessz T, Seeger W, Wilke A, Koob R, Lutz F, Drenckhahn D (1988) Bacterial exotoxins and endothelial permeability for water and albumin in vitro. Am J Physiol 255:C368Google Scholar
  77. Tarbell JM, Qiu Y (2000) Arterial wall mass transport: the possible role of blood phase resistance in the localization of arterial disease. In: Bronzino JD (ed) The biomedical engineering handbook, 2nd edn. CRC Press, New YorkGoogle Scholar
  78. Tarbell JM (2003) Mass transport in arteries and the localization of atherosclerosis. Annu Rev Biomed Eng 5:79Google Scholar
  79. Tarbell JM, Weinbaum S, Kamm RD (2005) Cellular fluid mechanics and mechanotransduction. Ann Biomed Eng 33:1719Google Scholar
  80. Tarbell JM (2010) Shear stress and the endothelial transport barrier. Cardiovasc Res 87:320Google Scholar
  81. Tedgui A, Lever MJ (1984) Filtration through damaged and undamaged rabbit thoracic aorta. Am J Physiol 247:H784Google Scholar
  82. Turner MR, Clough G, Michel CC (1983) The effects of cationised ferritin and native ferritin upon the filtration coefficient of single frog capillaries. Evidence that proteins in the endothelial cell coat influence permeability. Microvasc Res 25:205Google Scholar
  83. Turner MR (1992) Flows of liquid and electrical current through monolayers of cultured bovine arterial endothelium. J Physiol 449:1Google Scholar
  84. Valenta DT, Bulgrien JJ, Banka CL, Curtiss LK (2006) Overexpression of human ApoAI transgene provides long-term atheroprotection in LDL receptor-deficient mice. Atherosclerosis 189:255Google Scholar
  85. van den Berg BM, Vink H, Spaan JAE (2003) The endothelial glycocalyx protects against myocardial edema. Circ Res 92:592Google Scholar
  86. van den Berg BM, Spaan JAE, Rolf TM, Vink H (2006) Atherogenic region and diet diminish glycocalyx dimension and increase intima-to-media ratios at murine carotid artery bifurcation. Am J Physiol Heart Circ Physiol 290:915Google Scholar
  87. van Haaren PMA, Van Bavel E, Vink H, Spaan JAE (2003) Localization of the permeability barrier to solutes in isolated arteries by confocal microscopy. Am J Physiol Heart Circ Physiol 285:H2848Google Scholar
  88. Van Teeffelen JW, Brands J, Stroes ES, Vink H (2007) Endothelial glycocalyx: sweet shield of blood vessels. Trends Cardiovas Med 17:101Google Scholar
  89. Venturoli M, Maddalenasperotto M, Kranenburg M, Smit B (2006) Mesoscopic models of biological membranes. Phys Rep 437:1Google Scholar
  90. Vincent PE (2009) A cellular scale study of low density lipoprotein concentration polarisation in arteries, PhD thesis. Imperial College, LondonGoogle Scholar
  91. Vincent PE, Sherwin SJ, Weinberg PD (2009) The effect of a spatially heterogeneous transmural water flux on concentration polarization of low density lipoprotein in arteries. Biophys J 96:3102Google Scholar
  92. Vincent PE, Sherwin SJ, Weinberg PD (2010) The effect of the endothelial glycocalyx layer on concentration polarisation of low density lipoprotein in arteries. J Theor Biol 265:1MathSciNetGoogle Scholar
  93. Vink H, Duling BR (1996) Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries. Circ Res 79:581Google Scholar
  94. Vink H, Duling BR (2000) Capillary endothelial surface layer selectively reduces plasma solute distribution volume. Am J Physiol Heart Circ Physiol 278:H285Google Scholar
  95. Wada S, Karino T (1999) Theoretical study on flow-dependent concentration polarization of low density lipoproteins at the luminal surface of a straight artery. Biorheology 36:207Google Scholar
  96. Wada S, Karino T (2002) Theoretical prediction of low-density lipoproteins concentration at the luminal surface of an artery with a multiple bend. Ann Biomed Eng 30:778Google Scholar
  97. Wada S, Koujiya M, Karino T (2002) Theoretical study of the effect of local flow disturbances on the concentration of low-density lipoproteins at the luminal surface of end-to-end anastomosed vessels. Med Biol Eng Comput 40:576Google Scholar
  98. Wada S, Karino T (2002) Prediction of LDL concentration at the luminal surface of a vascular endothelium. Biorheology 39:331Google Scholar
  99. Wakeman W, Salpadoru N, Caro C (1976) Diffusion coefficients for protein molecules in blood serum. Atherosclerosis 25:225Google Scholar
  100. Wang G, Deng X, Guidoin R (2003) Concentration polarization of macromolecules in canine carotid arteries and its implication for the localization of atherogenesis. J Biomech 36:45Google Scholar
  101. Wei D, Wang G, Tang C, Qiu J, Zhao J, Gregersen H, Deng L (2012) Upregulation of SDF-1 is associated with atherosclerosis lesions induced by LDL concentration polarization. Ann Biomed Eng 40:1018 Google Scholar
  102. Weinbaum S (1997) Whitaker distinguished lecture: models to solve mysteries in biomechanics at the cellular level; a new view of fiber matrix layers. Ann Biomed Eng 26:627Google Scholar
  103. Weinbaum S, Zhang X, Han Y, Vink H, Cowin SC (2003) Mechanotransduction and flow across the endothelial glycocalyx. Proc Natl Acad Sci USA 100:7988Google Scholar
  104. Weinbaum S, Tarbell JM, Damiano ER (2007) The structure and function of the endothelial glycocalyx layer. Annu Rev Biomed Eng 9:121Google Scholar
  105. Wolinsky H, Glagov S (1967) Nature of species differences in the medial distribution of aortic vasa vasorum in mammals. Circ Res 20:409Google Scholar
  106. Woolf N (1990) Pathology of atherosclerosis. Br Med Bull 46:960Google Scholar
  107. Yin Y, Arkhipov A, Schulten K (2009) Simulations of membrane tubulation by lattices of amphiphysin N-bar domains. Structure 17:882Google Scholar
  108. Zeman LJ, Zydney AL (1996) Microfiltration and ultrafiltration: principles and applications. CRC Press, Boca RatonGoogle Scholar
  109. Zhang Z, Deng X, Fan Y, Li D (2007) Ex vitro experimental study on concentration polarization of macromolecules (LDL) at an arterial stenosis. Sci China Ser C 50:486Google Scholar
  110. Zydney AL (1997) Stagnant film model for concentration polarization in membrane systems. J Membrane Sci 130:275Google Scholar

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of AeronauticsImperial College LondonSouth Kensington, LondonUK
  2. 2.Department of BioengineeringImperial College LondonSouth Kensington, LondonUK

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