Skip to main content
Log in

Theoretical Prediction of Low-Density Lipoproteins Concentration at the Luminal Surface of an Artery with a Multiple Bend

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

To elucidate the mechanisms of localization of atherosclerotic lesions in man, the effects of various physical and hemodynamic factors on transport of atherogenic low-density lipoproteins (LDL) from flowing blood to the wall of an artery with a multiple bend were studied theoretically by means of a computer simulation under the conditions of a steady flow. It was found that due to a semipermeable nature of an arterial wall to plasma, flow-dependent concentration polarization of LDL occurred at the luminal surface of the vessel, creating a region of high LDL concentration distal to the apex of the inner wall of each bend where the flow was locally disturbed by the formation of secondary and recirculation flows and where wall shear stresses were low. The highest surface concentration of LDL occurred distal to the acute second bend where atherosclerotic intimal thickening developed. At a Re0=500, the values calculated using estimated diffusivities of LDL in whole blood and plasma were respectively 35.1% and 15.6% higher than that in the bulk flow. The results are consistent with our hypothesis that the localization of atherosclerotic lesions results from the flow-dependent concentration polarization of LDL which creates locally a hypercholesterolemic environment even in normocholesterolemic subjects, thus augmenting the uptake of LDL by vascular endothelial cells existing at such sites. © 2002 Biomedical Engineering Society.

PAC2002: 8719Uv, 8719Xx, 8714Ee, 8716Uv

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Asakura, T., and T. Karino. Flow patterns and spatial distribution of atherosclerotic lesions in human coronary arteries. Circ. Res. 66:1045-1066, 1990.

    Google Scholar 

  2. Barker, S. G. E., L. C. Tilling, G. C. Miller, J. E. Beesley, G. Fleetwood, G. T. Stavri, P. A. Baskerville, and J. F. Martin. The adventitia and atherogenesis: Removal initiates intimal proliferation in the rabbit which regress on generation of a "neoadventitia." Arteriosclerosis (Dallas) 105:131-144, 1994.

    Google Scholar 

  3. Bierman, E. L. Atherosclerosis and aging. Fed. Proc. 37:2832-2836, 1978.

    Google Scholar 

  4. Bratzler, B. L., G. M. Chisolm, C. K. Colton, K. A. Smith, and R. S. Lees. The distribution of labeled low-density lipoproteins across the rabbit thoracic aorta in vivo. Arteriosclerosis (Dallas) 28:289-307, 1977.

    Google Scholar 

  5. Brooks, A. N., and T. J. R. Hughes. Streamline upwind/Petrov-Galerkin formulations for convection dominated flows with particular emphasis on the incompressible Navier-Stokes equations. Comput. Methods Appl. Mech. Eng. 32:199-259, 1982.

    Google Scholar 

  6. Caro, C. G., J. M. Fitz-Gerald, and R. C. Schroter. Arterial wall shear and distribution of early atheroma in man. Nature (London) 223:1159-1161, 1969.

    Google Scholar 

  7. Caro, C. G., J. M. Fitz-Gerald, and R. C. Schroter. Atheroma and arterial wall shear. Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis. Proc. R. Soc. London, Ser. B 177:109-159, 1971.

    Google Scholar 

  8. Crossley, J. M., S. P. Spraggs, J. M. Creeth, N. Noble, and J. Slack. Anomalous temperature dependence on frictional coefficients: diffusion and sedimentation measurement of lowdensity lipoproteins, albumin, and polystyrene latex. Biopolymers 21:233-248, 1982.

    Google Scholar 

  9. Deng, X., Y. Marois, T. How, Y. Merhi, M. King, R. Guidoin, and T. Karino. Luminal surface concentration of lipoprotein (LDL) and its effect on the wall uptake of cholesterol by canine carotid arteries. J. Vasc. Surg. 21:135-145, 1995; 22:9A, 1995; 22:648, 1995;.

    Google Scholar 

  10. Dintenfass, L., and S. Kammer. Plasma viscosity in 615 subjects. Effect of fibrinogen, globulin, and cholesterol in normals, peripheral vascular disease retinopathy, and melanoma. Biorheology 14:247-251, 1977.

    Google Scholar 

  11. Fox, B., K. James, B. Morgan, and A. Seed. Distribution of fatty and fibrous plaques in young human coronary arteries. Arteriosclerosis (Dallas) 41:337-347, 1982.

    Google Scholar 

  12. Friedman, M. H., J. M. Henderson, J. A. Aukerman, and P. A. Clingan. Effect of periodic alterations in shear on vascular macromolecular uptake. Biorheology 37:265-77, 2000.

    Google Scholar 

  13. Fry, D. L. Aortic Evans blue dye accumulation: Its measurement and interpretation. Am. J. Physiol. 232:H204-H222, 1977.

    Google Scholar 

  14. Grøttum, P., A. Svindland, and L. Walløe. Localization of atherosclerotic lesions in the bifurcation of the main left coronary artery. Arteriosclerosis (Dallas) 47:55-62, 1983.

    Google Scholar 

  15. Hoff, H. F., and W. D. Wagner. Plasma low density lipoprotein accumulation in aortas of hypercholesterolemic swine correlates with modifications in aortic glycosaminoglycan composition. Arteriosclerosis (Dallas) 61:231-236, 1986.

    Google Scholar 

  16. Ishibashi, H., M. Sunamura, and T. Karino. Flow patterns and preferred sites of intimal thickening in end-to-end anastomosed vessels. Surgery (St. Louis) 117:409-420, 1995.

    Google Scholar 

  17. Jackson, R. L., J. D. Morrisett, and A. M. Gotto. Lipoprotein structure and metabolism. Physiol. Rev. 56:259-316, 1976.

    Google Scholar 

  18. Jo, H., R. O. Dull, T. M. Hollis, and J. M. Tarbell. Endothelial albumin permeability is shear dependent, time dependent, and reversible. Am. J. Physiol. 260:H1992-1996, 1991.

    Google Scholar 

  19. Karino, T. Microscopic structure of disturbed flows in the arterial and venous systems, and its implication in the localization of vascular diseases. Int. Angiol. 5:297-313, 1986.

    Google Scholar 

  20. Karino, T., and X. Deng. Lipoprotein concentration at the blood/endothelium boundary and its implications for the pathogenesis of vascular diseases. J. Jpn. Coll. Angiol. 30:710, 1990.

    Google Scholar 

  21. Ku, D. N., D. P. Giddens, C. K. Zarins, and S. Glagov. Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low and oscillating shear stress. Arteriosclerosis (Dallas) 5:293-302, 1985.

    Google Scholar 

  22. Levesque, M. J., and R. M. Nerem. The elongation and orientation of cultured endothelial cells in response to shear stress. J. Biomech. Eng. 107:341-347, 1985.

    Google Scholar 

  23. Ma, P., X. Li, and D. N. Ku. Convective mass transfer at the carotid bifurcation. J. Biomech. 30:565-571, 1997.

    Google Scholar 

  24. Motomiya, M., and T. Karino. Flow patterns in the human carotid artery bifurcation. Stroke 15:50-56, 1984.

    Google Scholar 

  25. Ojha, M. Spatial and temporal variations of wall shear stress within an end-to-side arterial anastomosis model. J. Biomech. 26:1377-1388, 1993.

    Google Scholar 

  26. Rappitsch, G., and K. Perktold. Pulsatile albumin transport in large arteries: A numerical simulation study. J. Biomech. Eng. 118:511-519, 1996.

    Google Scholar 

  27. Roach, M. R., J. Fletcher, and J. F. Cornhill. The effect of the duration of cholesterol feeding on the development of sudanophilic lesions in the rabbit aorta. Arteriosclerosis (Dallas) 25:1-11, 1976.

    Google Scholar 

  28. Ross, R., and L. Harker. Hyperlipidemia and atherosclerosis. Chronic hyperlipidemia initiates and maintains lesions by endothelial cell desquamation and lipid accumulation. Science 193:1094-1100, 1976.

    Google Scholar 

  29. Sabbah, H. N., F. Khaja, J. F. Brymer, E. T. Hawkins, and P. D. Stein. Blood velocity in the right coronary artery: Relation to the distribution of atherosclerotic lesions. Am. J. Cardiol. 53:1008-1012, 1984.

    Google Scholar 

  30. Schwenke, D. C., and T. E. Carew. Initiation of atherosclerotic lesions in cholesterol-fed rabbits. I. Focal increases in arterial LDL concentration precede development of fatty streak lesions. Arteriosclerosis (Dallas) 9:895-907, 1989.

    Google Scholar 

  31. Small, D. M. Progression and regression of atherosclerotic lesions. Insights from lipid physical biochemistry. Arteriosclerosis (Dallas) 8:103-129, 1988.

    Google Scholar 

  32. Spring, P. M., and H. F. Hoff. LDL accumulation in the grossly normal human iliac bifurcation and common iliac arteries. Exp. Molec. Pathol. 51:179-85, 1989.

    Google Scholar 

  33. Svindland, A. Localization of atherosclerotic lesions in three cerebral arterial bifurcations. Acta. Path. Microbiol. Immunol. Scand. Sect. A 92:177-183, 1984.

    Google Scholar 

  34. Tedgui, A., and M. J. Lever. Filtration through damaged and undamaged rabbit thoracic aorta. Am. J. Physiol. 247:H784-H791, 1984.

    Google Scholar 

  35. Truskey, G. A., W. L. Roberts, R. A. Herrmann, and R. A. Malinauskas. Measurement of endothelial permeability to 125I-low density lipoproteins in rabbit arteries by use of en face preparations. Circ. Res. 71:883-897, 1992.

    Google Scholar 

  36. Vasile, E., M. Simionescu, and N. Simionescu. Visualization of the binding, endocytosis, and transcytosis of low-density lipoprotein in the arterial endothelium in situ. J. Cell Biol. 96:1677-1689, 1983.

    Google Scholar 

  37. Wada, S., M. Kaichi, and T. Karino. Changes in water filtration velocity and wall structure of the rabbit common carotid artery after removal of the adventitia. JSME Int. J., Ser. C 44:996-1004, 2001.

    Google Scholar 

  38. Wada, S., and T. Karino. Theoretical study on flow-dependent concentration polarization of low density lipoproteins at the luminal surface of a straight artery. Biorheology 36:207-223, 1999.

    Google Scholar 

  39. Wada, S., and T. Karino. Computational study on LDL transport from flowing blood to arterial walls. In: Clinical Application of Computational Mechanics to the Cardiovascular System, edited by T. Yamaguchi. Tokyo: Springer, 2000, pp. 157-173.

    Google Scholar 

  40. Wada, S., and T. Karino. Prediction of LDL concentration at the luminal surface of a vascular endothelium. Biorheology (In press).

  41. Wada, S., M. Kojiya, and T. Karino. The effect of creating a moderate stenosis on the localization of intimal thickening in the common carotid artery of the rabbit fed on a cholesterolrich diet. JSME Int. J., Ser. C 44:1021-1030, 1981.

    Google Scholar 

  42. Weinbaum, S., G. Tzeghai, P. Ganatos, R. Pfeffer, and S. Chien. Effect of cell turnover and leaky junctions on arterial macromolecular transport. Am. J. Physiol. 248:H945-H960, 1985.

    Google Scholar 

  43. Wilens, S. L., and R. T. McCluskey. The comparative filtration properties of excised arteries and veins. Am. J. Med. 224:540-547, 1952.

    Google Scholar 

  44. Zarins, C. K., D. P. Giddens, B. K. Bharadvaj, V. S. Sottiurai, R. F. Mabon, and S. Glagov. Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ. Res. 53:502-514, 1983.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wada, S., Karino, T. Theoretical Prediction of Low-Density Lipoproteins Concentration at the Luminal Surface of an Artery with a Multiple Bend. Annals of Biomedical Engineering 30, 778–791 (2002). https://doi.org/10.1114/1.1495868

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1114/1.1495868

Navigation