Modeling the pathogenesis of early-stage atherosclerosis following ionizing radiation exposure: A three-dimensional numerical study using COMSOL

Abstract

According to a World Health Organization 2012 report, ischemic heart disease and stroke top the list of the ten leading causes of death in the world. Atherosclerosis, a major cause of both diseases, initiates with damage to the endothelium of the arterial wall and leads to the formation of plaque buildup within the artery. Many lifestyle factors contribute to the development of atherosclerosis including history of hypertension, smoking, and high cholesterol. Less investigated is the contribution of radiation-induced cellular death in the initiation of atheroma. This research is a continuation of a 2009 study [1] in which Little et al. developed a nonlinear system of reaction-diffusion equations on a 2D annulus to model cardiovascular disease after low-dose radiation exposure. However, this model was limited due to simplifications in the biology and due to system instabilities, as the concentration of several species blew up after brief perturbation. We used COMSOL Multiphysics v. 4.4 [2], a finite element analysis software package, to resolve any system instabilities and introduce cell survival curves within the initial conditions. The results of this model can be used to predict the rate of lesion formation hours or days post-exposure in those exposed to radiological incidents (e.g. nuclear facility breach or terrorism) or therapeutic doses of ionizing radiation. Our work found that there is an increase in plaque size, and thus increased risk of an adverse cardiac event, associated with absorbed doses of greater than or equal to 2.2 Gray (Gy). These results have tremendous implications on current radiotherapy routines, which typically employ daily conventional or hypo-fractionated doses of 1.8-2.0 Gy, but can deliver upwards of 2.0 Gy for certain regimens. We expect that investigators and medical professionals will be able to modify the radiation dose and time scale in order to determine the effects on nine different phenomena involved in the initiation of atherosclerosis.