title: An in silico study on the role of smooth muscle cell migration in neointimal formation after coronary stenting.
abstract: Excessive migration and proliferation of smooth muscle cells (SMCs) has been observed as a major factor contributing to the development of in-stent restenosis after coronary stenting. Building upon the results from in vivo experiments, we formulated a hypothesis that the speed of the initial tissue re-growth response is determined by the early migration of SMCs from the injured intima. To test this hypothesis, a cellular Potts model of the stented artery is developed where stent struts were deployed at different depths into the tissue. An extreme scenario with a ruptured internal elastic lamina was also considered to study the role of severe injury in tissue re-growth. Based on the outcomes, we hypothesize that a deeper stent deployment results in on average larger fenestrae in the elastic lamina, allowing easier migration of SMCs into the lumen. The data also suggest that growth of the neointimal lesions owing to SMC proliferation is strongly dependent on the initial number of migrated cells, which form an initial condition for the later phase of the vascular repair. This mechanism could explain the in vivo observation that the initial rate of neointima formation and injury score are strongly correlated.
authors.affiliation: Computational Science Laboratory, Informatics Institute, University of Amsterdam, Amsterdam, The Netherlands h.tahir@cwi.nl.
authors.forename: Hannan
authors.initials: H
authors.lastname: Tahir
authors.affiliation: Computational Science Laboratory, Informatics Institute, University of Amsterdam, Amsterdam, The Netherlands Life Sciences Group, Centrum Wiskunde and Informatica, Amsterdam, The Netherlands.
authors.forename: Ioana
authors.initials: I
authors.lastname: Niculescu
authors.affiliation: Computational Science Laboratory, Informatics Institute, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Carles
authors.initials: C
authors.lastname: Bona-Casas
authors.affiliation: Life Sciences Group, Centrum Wiskunde and Informatica, Amsterdam, The Netherlands Mathematical Institute, Leiden University, Leiden, The Netherlands.
authors.forename: Roeland M H
authors.identifier: http://orcid.org/0000-0002-6152-687X
authors.initials: RM
authors.lastname: Merks
authors.affiliation: Computational Science Laboratory, Informatics Institute, University of Amsterdam, Amsterdam, The Netherlands National Research University ITMO, Saint Petersburg, Russia.
authors.forename: Alfons G
authors.initials: AG
authors.lastname: Hoekstra
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D003198:Computer Simulation; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008955:Models, Cardiovascular; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D058426:Neointima / Q000378:metabolism* / Q000473:pathology; D015607:Stents
keywords: cellular Potts model; in-stent restenosis; internal elastic lamina; smooth muscle cells; stent deployment