Published Online
on May 12, 2003

A more recent version of this article appeared on June 3, 2003

This Article Full Text (PDF) All Versions of this Article: 107/21/2741    most recent 01.CIR.0000066914.95878.6Dv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carlier, S. G. Articles by Krams, R. Search for Related Content PubMed PubMed Citation Articles by Carlier, S. G. Articles by Krams, R. Pubmed/NCBI databases Substance via MeSH Related Collections Restenosis

Submitted on November 27, 2002
Revised on February 19, 2003
Accepted on February 25, 2003

Augmentation of Wall Shear Stress Inhibits Neointimal Hyperplasia After Stent Implantation. Inhibition Through Reduction of Inflammation?

Stéphane G. Carlier MD, PhD, Luc C.A. van Damme BSc, Casper P. Blommerde MD, Jolanda J. Wentzel PhD, Glenn van Langehove MD, PhD, Stephan Verheye MD, PhD, Mark M. Kockx MD, PhD, Michiel W.M. Knaapen MD, PhD, Caroline Cheng MSc, Frank Gijsen PhD, Dirk J. Duncker MD, PhD, Nikos Stergiopulos PhD, Cornelis J. Slager PhD, Patrick W. Serruys MD, PhD, and Rob Krams MD, PhD^*

From the Thoraxcentre, Erasmus Medical Center Rotterdam (S.G.C., L.C.A.v.D., C.P.B., F.G., D.J.D., C.J.S., P.W.S., R.K.) and Interuniversity Institute of Cardiology of the Netherlands (J.J.W., C.C.), Utrecht, Netherlands; Middelheim Hospital (G.v.L., S.V., M.M.K.) and HistogeneX (M.W.M.K.), Antwerp, Belgium; and Ecole Polytechnique, Lausanne, Switzerland (N.S.).

^* To whom correspondence should be addressed. E-mail: r.krams{at}erasmusmc.nl.

Background--Low wall shear stress (WSS) increases neointimal hyperplasia (NH) in vein grafts and stents. We studied the causal relationship between WSS and NH formation in stents by locally increasing WSS with a flow divider (Anti-Restenotic Diffuser, Endoart SA) placed in the center of the stent.

Methods and Results--In 9 rabbits fed a high-cholesterol diet for 2 months to induce endothelial dysfunction, 18 stents were implanted in the right and left external iliac arteries (1 stent per vessel). Lumen diameters were measured by quantitative angiography before and after implantation and at 4-week follow-up, at which time, macrophage accumulation and interruption of the internal elastic lamina was determined. Cross sections of stent segments within the ARED (S+ARED), outside the ARED (S[minus]ARED), and in corresponding segments of the contralateral control stent (SCTRL) were analyzed. Changes in WSS induced by the ARED placement were derived by computational fluid dynamics. Computational fluid dynamics analysis demonstrated that WSS increased from 0.38 to 0.82 N/m² in the S+ARED immediately after ARED placement. This augmentation of shear stress was accompanied by (1) lower mean late luminal loss by quantitative angiography ([minus]0.23±0.22 versus [minus]0.58±0.30 mm, P=0.02), (2) reduction in NH (1.48±0.58, 2.46±1.25, and 2.36±1.13 mm², P<0.01, respectively, for S+ARED, S[minus]ARED, and SCTRL), and (3) a reduced inflammation score and a reduced injury score. Increments in shear stress did not change the relationship between injury score and NH or between inflammation score and NH.

Conclusions--The newly developed ARED flow divider significantly increases WSS, and this local increment in WSS is accompanied by a local reduction in NH and a local reduction in inflammation and injury. The present study is therefore the first to provide direct evidence for an important modulating role of shear stress in in-stent neointimal hyperplasia.

Key words: shear stress • restenosis • stents • cells • inflammation

This article has been cited by other articles:

				X. Liu, H. Doi, A. Maehara, G. S. Mintz, J. de Ribamar Costa Jr, K. Sano, G. Weisz, G. D. Dangas, A. J. Lansky, E. M. Kreps, et al. A Volumetric Intravascular Ultrasound Comparison of Early Drug-Eluting Stent Thrombosis Versus Restenosis J. Am. Coll. Cardiol. Intv., May 1, 2009; 2(5): 428 - 434. [Abstract] [Full Text] [PDF]

				Y. Honda and P. J. Fitzgerald Frontiers in Intravascular Imaging Technologies Circulation, April 15, 2008; 117(15): 2024 - 2037. [Full Text] [PDF]

				C. Cheng, D. Tempel, A. Oostlander, F. Helderman, F. Gijsen, J. Wentzel, R. van Haperen, D. B. Haitsma, P. W. Serruys, A. F.W. van der Steen, et al. Rapamycin modulates the eNOS vs. shear stress relationship Cardiovasc Res, April 1, 2008; 78(1): 123 - 129. [Abstract] [Full Text] [PDF]

				Y. Zhang, X. He, X. Chen, H. Ma, D. Liu, J. Luo, Z. Du, Y. Jin, Y. Xiong, J. He, et al. Enhanced External Counterpulsation Inhibits Intimal Hyperplasia by Modifying Shear Stress Responsive Gene Expression in Hypercholesterolemic Pigs Circulation, July 31, 2007; 116(5): 526 - 534. [Abstract] [Full Text] [PDF]

				F. Alfonso Haemodynamic findings after drug-eluting stenting: expected, provocative, or challenging? Eur. Heart J., August 1, 2006; 27(15): 1764 - 1766. [Full Text] [PDF]

				M. O. Platt, R. F. Ankeny, and H. Jo Laminar Shear Stress Inhibits Cathepsin L Activity in Endothelial Cells Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1784 - 1790. [Abstract] [Full Text] [PDF]

				A. Kondyurin, V. Romanova, V. Begishev, I. Kondyurina, R. Guenzel, and M. F. Maitz Crosslinked Polyurethane Coating on Vascular Stents for Enhanced X-ray Contrast Journal of Bioactive and Compatible Polymers, January 1, 2005; 20(1): 77 - 93. [Abstract] [PDF]

				K. Tsuda, I. Nishio, P. Piatti, L. D. Monti, E. Setola, P. Lucotti, E. Galluccio, A. Origgi, C. Di Mario, F. Sgura, et al. Hyperinsulinemia, Hyperleptinemia, and Nitric Oxide in the Regulation of Membrane Micoviscosity * Response Circulation, April 27, 2004; 109(16): e199 - e200. [Full Text] [PDF]

				S. M Wasserman and J. N Topper Adaptation of the endothelium to fluid flow: in vitro analyses of gene expression and in vivo implications Vascular Medicine, February 1, 2004; 9(1): 35 - 45. [Abstract] [PDF]