Abstract
Previous numerical simulations on low-density lipoprotein (LDL) concentration polarization in the arterial system indicated that LDL concentration polarization might play an important role in the genesis and development of atherosclerosis. To date, no in vivo experiments have examined this question directly, and the molecular mechanisms are unknown. In this study, ten rabbits were treated with gel–silica loop to develop a defined local stenosis in the straight segment of the left carotid artery. Both numerical simulation and experiment measurements showed that the concentration of LDL was about 35% higher at the blood/arterial wall interface than in the lumen on the distal side of the stenosis. Atherosclerotic lesions with abundant lipid deposits were observed and stromal derived factor-1 (SDF-1) was detected at the distal end of the stenosis, while the straight segment was plaque-free. In vitro studies demonstrated that LDL-induced SDF-1 expression in endothelial cells and increased monocyte adhesion to endothelial cells in a dose-dependent manner. The adhesion was suppressed when endothelial cells were pretreated with SDF-1 antibody. These results suggested LDL concentration polarization contributed to the localization of atherosclerosis and to the expression of SDF-1. In turn, SDF-1 facilitated plaque formation.
Similar content being viewed by others
References
Abi-Younes, S., A. Sauty, F. Mach, G. K. Sukhova, P. Libby, and A. D. Luster. The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques. Circ. Res. 86:131–138, 2000.
Chatzizisis, Y. S., A. U. Coskun, M. Jonas, E. R. Edelman, C. L. Feldman, and P. H. Stone. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular and vascular behavior. J. Am. Coll. Cardiol. 49:2379–2393, 2007.
de la Sierra, A., and M. Larrousse. Endothelial dysfunction is associated with increased levels of biomarkers in essential hypertension. J. Hum. Hypertens. 24:373–379, 2010.
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.
Ding, Z., Y. Fan, and X. Deng. Effect of LDL concentration polarization on the uptake of LDL by human endothelial cells and smooth muscle cells co-cultured. Acta Biochim. Biophys. Sin. (Shanghai) 4:146–153, 2009.
Ding, Z., Y. Fan, X. Deng, A. Sun, and H. Kang. 3,3′-Dioctadecylindocarbocyanine-low-density lipoprotein uptake and flow patterns in the rabbit aorta-iliac bifurcation under three perfusion flow conditions. Exp. Biol. Med. (Maywood) 235:1062–1071, 2010.
Fatouraee, N., X. Deng, A. De Champlain, and R. Guidoin. Concentration polarization of low density lipoproteins (LDL) in the arterial system. Ann. N. Y. Acad. Sci. 858:137–146, 1998.
Geisel, J., V. Jödden, R. Obeid, J. P. Knapp, M. Bodis, and W. Herrmann. Stimulatory effect of homocysteine on interleukin-8 expression in human endothelial cells. Clin. Chem. Lab. Med. 41:1045–1048, 2003.
Hsu, S. W., J. C. Chaloupka, J. A. Feekes, M. D. Cassell, and Y. F. Cheng. In vitro studies of the neuroform microstent using transparent human intracranial arteries. AJNR Am. J. Neuroradiol. 27:1135–1139, 2006.
Jiang, T., G. Wang, J. Qiu, L. Luo, and G. Zhang. Preparation and biocompatibility of polyvinyl alcohol—small intestinal submucosa hydrogel membranes. J. Med. Biol. Eng. 29(2):102–107, 2009.
Kim, J. A., J. A. Berlianer, and J. L. Nadler. AngiotensinII increase monocyte binding to endothelial cells. J. Biochem. Biophys. Res. Commun. 226:862–868, 1996.
Li, M. X., J. J. Beech-Brandt, L. R. John, P. R. Hoskins, and W. J. Easson. Numerical analysis of pulsatile blood flow and vessel wall mechanics in different degrees of stenoses. J. Biomech. 40:3715–3724, 2007.
Liu, K. K. Y., and K. Dorovini-Zis. Regulation of CXCL12 and CXCR4 expression by human brain endothelial cells and their role in CD4+ and CD8+ T cell adhesion and transendothelial migration. J. Neuroimmunol. 215:49–64, 2009.
Liu, X., Y. B. Fan, X. Y. Deng, and F. Zhan. Effect of non-Newtonian and pulsatile blood flow on mass transport in the human aorta. J. Biomech. 44:1123–1131, 2011.
Liu, B., and D. Tang. Influence of non-Newtonian properties of blood on the wall shear stress in human atherosclerotic right coronary arteries. Mol. Cell. Biomech. 8:73–90, 2011.
Ma, X., Y. W. Hu, Z. C. Mo, X. X. Li, X. H. Liu, J. **ao, W. D. Yin, D. F. Liao, and C. K. Tang. NO-1886 up-regulates Niemann-Pick C1 protein (NPC1) expression through liver X receptor alpha signaling pathway in THP-1 macrophage-derived foam cells. Cardiovasc. Drugs Ther. 23:199–206, 2009.
Malik, M., Y. Y. Chen, M. F. Kienzle, B. E. Tomkowicz, R. G. Collman, and A. Ptasznik. Monocyte migration and LFA-1-mediated attachment to brain microvascular endothelia is regulated by SDF-1 alpha through Lyn kinase. J. Immunol. 181:4632–4637, 2008.
Melchionna, R., D. Porcelli, A. Mangoni, D. Carlini, G. Liuzzo, G. Spinetti, A. Antonini, M. C. Capogrossi, and M. Napolitano. Laminar shear stress inhibits CXCR4 expression on endothelial cells: functional consequences for atherogenesis. FASEB J. 19:629–631, 2005.
Schwenke, D. C., and T. E. Carew. Initiation of atherosclerotic lesions in cholesterol-fed rabbits. II. Selective retention of LDL vs. selective increases in LDL permeability in susceptible sites of arteries. Arteriosclerosis 9:908–918, 1989.
Stary, H. C. Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Arteriosclerosis 9:119–132, 1989.
Stephan, Z. F., and E. C. Yurachek. Rapid fluorometric assay of LDL receptor activity by DiI-labeled LDL. J. Lipid Res. 34:325–330, 1993.
Lowry, O., N. Rosebrough, A. Farr, and R. Randall. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275, 1951.
Wada, S., and T. Karino. Theoretical prediction of low-density lipoproteins concentration at the luminal surface of an artery with a multiple bend. Ann. Biomed. Eng. 30:778–791, 2002.
Wang, G. X., X. Y. Deng, and R. Guidoin. Concentration polarization of macromolecules in canine carotid arteries and its implication for the localization of atherogenesis. J. Biomech. 36:45–51, 2003.
**aoyan, D. E. N. G., and W. A. N. G. Guixue. Concentration polarization of atherogenic lipids in the arterial system. Sci. China (Ser. C) 46:153–164, 2003.
Zernecke, A., E. Shagdarsuren, and C. Weber. Chemokines in atherosclerosis: an update. Arterioscler. Thromb. Vasc. Biol. 28:1897–1908, 2008.
Zhang, Z., X. Deng, Y. Fan, and D. Li. Ex vitro experimental study on concentration polarization of macromolecules (LDL) at an arterial stenosis. Sci. China Ser. C Life Sci. 50:486–491, 2007.
Acknowledgments
This research is supported by the National Natural Science Foundation of China (30970721, 30800449), the National Basic Research Program of China (Grant No. 2012CB945101). The assistance of Dr. X.-Y. Deng was greatly appreciated.
Author information
Authors and Affiliations
Corresponding author
Additional information
Associate Editor Joan Greve oversaw the review of this article.
Rights and permissions
About this article
Cite this article
Wei, D., Wang, G., Tang, C. et al. Upregulation of SDF-1 is Associated with Atherosclerosis Lesions Induced by LDL Concentration Polarization. Ann Biomed Eng 40, 1018–1027 (2012). https://doi.org/10.1007/s10439-011-0486-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10439-011-0486-z