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(Circulation. 2001;104:91.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Shear-Stress and Wall-Stress Regulation of Vascular Remodeling After Balloon Angioplasty

Effect of Matrix Metalloproteinase Inhibition

Jolanda J. Wentzel, PhD; Jeroen Kloet, Msc; Ivan Andhyiswara, Msc; Jan A. F. Oomen, Msc; Johan C. H. Schuurbiers, Bsc; Bart J. G. L. de Smet, MD, PhD; Mark J. Post, MD, PhD; Dominique de Kleijn, PhD; Gerard Pasterkamp, MD, PhD; Cornelius Borst, MD, PhD; Cornelis J. Slager, PhD; Rob Krams, MD, PhD

From the Department of Cardiology, Thoraxcenter Rotterdam (J.J.W., J.K., I.A., J.A.F.O., J.C.H.S., C.J.S., R.K.); Inter University Cardiology Institute of the Netherlands (J.J.W., B.J.G.L.d.S., D.d.K., G.P.); and Experimental Cardiology Utrecht (B.J.G.L.d.S., M.J.P., D.d.K., G.P., C.B.), the Netherlands.

Correspondence to R. Krams, MD, PhD, Department of Cardiology EE2369, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands. E-mail krams{at}tch.fgg.eur.nl

Background—Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiological conditions VR is associated with normalization of shear stress (SS) and wall stress (WS), after PTA the role of SS and WS in VR is unknown. Furthermore, whereas matrix metalloproteinase inhibition (MMPI) has been shown to modulate VR after PTA, its effect on the SS and WS control mechanisms after PTA is unknown.

Methods and Results—PTA was performed in external iliac arteries of 12 atherosclerotic Yucatan pigs, of which 6 pigs (7 vessels) received the MMPI batimastat and 6 pigs (10 vessels) served as controls. Before and after the intervention and at 6-week follow-up, intravascular ultrasound pullback was performed, allowing 3D reconstruction of the treated segment and computational fluid dynamics to calculate the media-bounded area and SS. WS was derived from the Laplace formula. Immediately after PTA, media-bounded area, WS, and SS changed by 20%, 16%, and -49%, respectively, in both groups. VR was predicted by SS and WS. In the control group, SS and WS had been normalized at follow-up with respect to the reference segment. In contrast, for the batimastat group, the SS had been normalized, but not the WS. The latter is attributed to an increase in wall area at follow-up.

Conclusions—Vascular remodeling after PTA is controlled by both SS and WS. MMPI inhibited the WS control system.

Key Words: stress • angioplasty • metalloproteinases

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