Modelling the effect of a functional endothelium on the development of in-stent restenosis

• Published in: PloS one Vol. 8; no. 6; p. e66138
• Main Authors: Tahir, Hannan, Bona-Casas, Carles, Hoekstra, Alfons G
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-06-2013; Public Library of Science (PLoS)
• Subjects: Angioplasty; Angioplasty, Balloon, Coronary - adverse effects; Animals; Arteries; Balloon angioplasty; Balloon treatment; Blood flow; Cellular manufacture; Computer Science; Computer Simulation; Coronary artery; Coronary Circulation; Coronary Restenosis - etiology; Coronary Restenosis - metabolism; Endothelial cells; Endothelium; Endothelium, Vascular - metabolism; Engineering; Hemodynamics; Implants; Inflammation; Lesions; Medicine; Models, Biological; Multi-scale models; Multiscale analysis; Muscles; Myocytes, Smooth Muscle - metabolism; Neointima - metabolism; Neointima - pathology; Nitric oxide; Nitrites - metabolism; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Qualitative analysis; Restenosis; Shear Strength; Shear stress; Smooth muscle; Stents; Stents - adverse effects; Stress analysis; Stress concentration; Stress distribution; Struts; Surgical implants; Swine; Time Factors; Two dimensional models; Veins & arteries
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0066138

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.