title: Neutrophil adhesion on endothelial cells in a novel asymmetric stenosis model: effect of wall shear stress gradients.
abstract: Leukocytes play a pivotal role in the progression of atherosclerosis. A novel three-dimensional in vitro asymmetric stenosis model was used to better investigate the role of local hemodynamics in the adhesion of leukocytes to an established plaque. The adhesion of a human promyelocytic cell line (NB4) on a human abdominal aortic endothelial cell (EC) monolayer was quantified. NB4 cells were circulated over TNF-alpha stimulated and nonstimulated ECs for 1 or 6 h at 1.25 or 6.25 dynes/cm(2) and compared to static conditions. Cytokine stimulation increased significantly EC expression of intercellular adhesion molecule and vascular cell adhesion molecule. Under static conditions, neutrophils adhered overall more than under flow, with decreased adhesion with increasing shear. Adhesion was significantly higher in the recirculation region distal to the stenosis than in the inlet. Preshearing the ECs decreased the expression of cell adhesion molecules in inflamed endothelium and significantly decreased adhesion. However, the ratio of adhesion between the recirculation zone and the inlet increased, hence exhibiting an increased regional difference. This work suggests an important role for neutrophil-EC interactions in the atherosclerotic process, especially in wall shear stress gradient regions. This is important clinically, potentially helping to explain plaque stability.
authors.affiliation: Department of Chemical Engineering, McGill University, Montreal, QC, Canada.
authors.forename: Leonie
authors.initials: L
authors.lastname: Rouleau
authors.forename: Ian B
authors.initials: IB
authors.lastname: Copland
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.forename: Rosaire
authors.initials: R
authors.lastname: Mongrain
authors.forename: Richard L
authors.initials: RL
authors.lastname: Leask
mesh_terms: D001012:Aorta, Abdominal / Q000503:physiopathology; D050197:Atherosclerosis / Q000503:physiopathology*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000032:analysis; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D033081:Shear Strength / Q000502:physiology*; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha
references.citation: Circulation. 2005 Jun 28;111(25):3481-8
references.pmid: 15983262
references.citation: Circ Res. 1993 Jun;72(6):1276-84
references.pmid: 8495555
references.citation: Microvasc Res. 1987 Jan;33(1):62-70
references.pmid: 3561268
references.citation: Am J Med Sci. 1998 Sep;316(3):169-75
references.pmid: 9749558
references.citation: Am J Physiol. 1997 Jan;272(1 Pt 2):H114-22
references.pmid: 9038929
references.citation: Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1350-8
references.pmid: 15191939
references.citation: J Biomed Eng. 1990 Nov;12(6):463-9
references.pmid: 2266741
references.citation: Arteriosclerosis. 1985 May-Jun;5(3):293-302
references.pmid: 3994585
references.citation: Eur Heart J. 2004 Jul;25(14):1197-207
references.pmid: 15246637
references.citation: Circulation. 1995 Sep 1;92(5):1355-74
references.pmid: 7648691
references.citation: Am J Physiol Cell Physiol. 2006 Dec;291(6):C1346-54
references.pmid: 16822941
references.citation: Ann Surg. 1985 Feb;201(2):115-31
references.pmid: 3155934
references.citation: Biomed Eng Online. 2009 Oct 28;8:30
references.pmid: 19863806
references.citation: Ann N Y Acad Sci. 2000 May;902:230-9; discussion 239-40
references.pmid: 10865843
references.citation: Br J Haematol. 1996 May;93(2):360-6
references.pmid: 8639429
references.citation: J Vasc Surg. 1994 Jun;19(6):1067-73
references.pmid: 8201708
references.citation: Int J Cardiovasc Imaging. 2001 Oct;17(5):371-81
references.pmid: 12025951
references.citation: J Biomech. 2001 Jan;34(1):95-103
references.pmid: 11425085
references.citation: Circulation. 1995 Aug 1;92(3):657-71
references.pmid: 7634481
references.citation: Circulation. 1998 Nov 10;98(19):2000-3
references.pmid: 9808596
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4478-85
references.pmid: 11296290
references.citation: Am J Med. 1999 Jul;107(1):85-97
references.pmid: 10403357
references.citation: Agents Actions Suppl. 1995;47:135-41
references.pmid: 7540353
references.citation: Thromb Res. 2002 Feb 15;105(4):325-9
references.pmid: 12031827
references.citation: J Clin Invest. 1997 Dec 1;100(11 Suppl):S61-5
references.pmid: 9413404
references.citation: Ann Biomed Eng. 2002 Mar;30(3):315-32
references.pmid: 12051617
references.citation: Med Eng Phys. 2008 Nov;30(9):1193-200
references.pmid: 18406195
references.citation: Clin Hemorheol Microcirc. 2008;39(1-4):113-9
references.pmid: 18503117
references.citation: J Interv Cardiol. 2003 Jun;16(3):267-72
references.pmid: 12800406
references.citation: J Vasc Interv Radiol. 2004 May;15(5):485-90
references.pmid: 15126659
references.citation: Blood. 2006 Mar 1;107(5):1933-42
references.pmid: 16293605
references.citation: J Leukoc Biol. 2000 Jul;68(1):47-57
references.pmid: 10914489
references.citation: Biochem Soc Trans. 2007 Nov;35(Pt 5):857-61
references.pmid: 17956232
references.citation: Circulation. 2002 Jan 22;105(3):297-303
references.pmid: 11804983
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14871-6
references.pmid: 15466704
references.citation: Nature. 2002 Dec 19-26;420(6917):868-74
references.pmid: 12490960
references.citation: Eur J Immunol. 1997 Aug;27(8):1942-51
references.pmid: 9295030
references.citation: Atherosclerosis. 2009 Nov;207(1):93-102
references.pmid: 19481207
references.citation: Lancet. 1989 Oct 21;2(8669):941-4
references.pmid: 2571862
references.citation: Microcirculation. 2008 May;15(4):311-23
references.pmid: 18464160
references.citation: Arterioscler Thromb Vasc Biol. 1995 Jan;15(1):2-10
references.pmid: 7538423
references.citation: Br J Pharmacol. 2005 Aug;145(8):1052-61
references.pmid: 15912126
references.citation: Nature. 1996 Jan 18;379(6562):266-9
references.pmid: 8538793
references.citation: Blood. 1994 Jul 1;84(1):294-302
references.pmid: 7517212
references.citation: Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H194-204
references.pmid: 15331359
references.citation: Blood. 1999 Oct 15;94(8):2725-34
references.pmid: 10515876
references.citation: Circulation. 2002 Mar 5;105(9):1135-43
references.pmid: 11877368
references.citation: Blood. 1996 Jan 15;87(2):613-7
references.pmid: 8555483