Shear-stress and wall-stress regulation of vascular remodeling after balloon angioplasty - Effect of matrix metalloproteinase inhibition

Background-Constrictive vascular remodeling (VR) is the most significant co mponent of restenosis after balloon angioplasty (PTA). Whereas in physiolog ical conditions VR is associated with normalization of shear stress (SS) an d wall stress (WS), after PTA the role of SS and WS in VR is unknown, Furth ermore, whereas matrix metalloproteinase inhibition (MMPI) has been shown t o modulate VR after PTA, its effect on the SS and WS control mechanisms aft er PTA is unknown. Methods and Results-PTA was performed in external iliac arteries of 12 athe rosclerotic Yucatan pigs, of which 6 pigs (7 vessels) received the MMPI bat imastat and 6 pigs (10 vessels) served as controls. Before and after the in tervention and at 6-week follow-up, intravascular ultrasound pullback was p erformed, allowing 3D reconstruction of the treated segment and computation al fluid dynamics to calculate the media-bounded area and SS. WS was derive d 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 b atimastat 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.