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.

A Comparison of Fully-Coupled 3D In-Stent Restenosis Simulations to In-vivo Data

“…Also, there exist several analytical and computational models of this process (Prendergast et al, 2003; Boyle et al, 2011, 2013; Keller et al, 2014; Nolan et al, 2014; Zahedmanesh et al, 2014), including those developed earlier by our group (Evans et al, 2008; Tahir et al, 2011, 2015; Amatruda et al, 2014). For example, Zahedmanesh et al (2014) use a two-dimensional (2D) finite element method (FEM) model of stent deployment coupled with an (also 2D) agent-based model of SMC proliferation and extracellular matrix (ECM) generation.…”

Prelamin A Accumulation Attenuates Rac1 Activity and Increases the Intrinsic Migrational Persistence of Aged Vascular Smooth Muscle Cells

“…Vascular smooth muscle cells (VSMCs) are the major cell type of the arterial wall and normally exist in a contractile, differentiated state to maintain vascular tone. However, contractile VSMCs are not terminally differentiated and retain the ability to dedifferentiate to a proliferative, migratory phenotype and enhanced VSMC motility is observed during development, vessel repair and in adverse vessel remodeling associated with restenosis and atherosclerosis [3,4,5]. VSMC phenotypic transition involves dramatic actin remodeling which is regulated by Rho GTPase signalling pathways [6,7].…”

Multiscale computing in the exascale era

“…This framework has been successfully tested on applications from several fields of science and technology (e.g. fusion [35,43], computational biology [35,44,45], biomedicine [17,35,36,[46][47][48][49][50][51][52], nanomaterial science [9,13,35], and hydrology [35]). The MMSF offers many benefits: a clear methodology, software and algorithm reuse, the possibility to couple new and legacy codes, heterogeneous distributed computing, and access to unprecedented computing resources [26].…”