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.
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REFERENCES
Asakura, T., and T. Karino. Flow patterns and spatial distribution of atherosclerotic lesions in human coronary arteries. Circ. Res. 66:1045-1066, 1990.
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.
Bierman, E. L. Atherosclerosis and aging. Fed. Proc. 37:2832-2836, 1978.
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.
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.
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.
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.
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.
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;.
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.
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.
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.
Fry, D. L. Aortic Evans blue dye accumulation: Its measurement and interpretation. Am. J. Physiol. 232:H204-H222, 1977.
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.
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.
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.
Jackson, R. L., J. D. Morrisett, and A. M. Gotto. Lipoprotein structure and metabolism. Physiol. Rev. 56:259-316, 1976.
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.
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.
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.
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.
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.
Ma, P., X. Li, and D. N. Ku. Convective mass transfer at the carotid bifurcation. J. Biomech. 30:565-571, 1997.
Motomiya, M., and T. Karino. Flow patterns in the human carotid artery bifurcation. Stroke 15:50-56, 1984.
Ojha, M. Spatial and temporal variations of wall shear stress within an end-to-side arterial anastomosis model. J. Biomech. 26:1377-1388, 1993.
Rappitsch, G., and K. Perktold. Pulsatile albumin transport in large arteries: A numerical simulation study. J. Biomech. Eng. 118:511-519, 1996.
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.
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.
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.
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.
Small, D. M. Progression and regression of atherosclerotic lesions. Insights from lipid physical biochemistry. Arteriosclerosis (Dallas) 8:103-129, 1988.
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.
Svindland, A. Localization of atherosclerotic lesions in three cerebral arterial bifurcations. Acta. Path. Microbiol. Immunol. Scand. Sect. A 92:177-183, 1984.
Tedgui, A., and M. J. Lever. Filtration through damaged and undamaged rabbit thoracic aorta. Am. J. Physiol. 247:H784-H791, 1984.
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.
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.
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.
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.
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.
Wada, S., and T. Karino. Prediction of LDL concentration at the luminal surface of a vascular endothelium. Biorheology (In press).
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.
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.
Wilens, S. L., and R. T. McCluskey. The comparative filtration properties of excised arteries and veins. Am. J. Med. 224:540-547, 1952.
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.
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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
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DOI: https://doi.org/10.1114/1.1495868