title: Modelling the effect of a functional endothelium on the development of in-stent restenosis.
abstract: Treatment of stenosed coronary arteries by balloon angioplasty and stenting results in arterial injury including severe damage to the endothelium at the site of treatment and initiates a complex cascade of inflammatory processes that may lead to the development of in-stent restenosis (ISR). Many clinical and biological factors involved in the progression of restenotic lesions have been studied in detail over the past few years but the mystery behind the pathophysiological mechanisms of this disease is still unresolved. In the present work, the effects of re-endothelialization and nitric oxide release on neointimal growth are investigated in-silico using a two dimensional multi-scale model of ISR. The effect of stent deployment depths on the development of ISR is studied as a function of time after stenting. Two dimensional domains were prepared by deploying bare metal stent struts at three different deployment depths into the tissue. Shear stress distribution on endothelial cells, obtained by blood flow simulations, was translated into nitric oxide production that keeps the smooth muscle cells in quiescent state. The cellular growth trends were plotted as a function of time and the data indicate a positive correlation between the neointimal growths and strut deployment depths in the presence of a functional endothelium, in qualitative agreement with in-vivo data. Additionally, no ISR is observed if a functional endothelium appears much earlier.
authors.affiliation: Computational Science, Informatics Institute, Faculty of Science, University of Amsterdam, Amsterdam, The Netherlands. h.tahir@uva.nl
authors.forename: Hannan
authors.initials: H
authors.lastname: Tahir
authors.forename: Carles
authors.initials: C
authors.lastname: Bona-Casas
authors.forename: Alfons G
authors.initials: AG
authors.lastname: Hoekstra
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D003198:Computer Simulation; D003326:Coronary Circulation; D023903:Coronary Restenosis / Q000209:etiology* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006439:Hemodynamics; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058426:Neointima / Q000378:metabolism / Q000473:pathology; D009573:Nitrites / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D033081:Shear Strength; D015607:Stents / Q000009:adverse effects*; D013552:Swine; D013997:Time Factors
chemical_list: D009573:Nitrites; D019408:Platelet Endothelial Cell Adhesion Molecule-1