How radiation influences atherosclerotic plaque development: a biophysical approach in ApoE ¯/¯ mice

Abstract

Atherosclerosis is the development of lipid-laden plaques in arteries and is nowadays considered as an inflammatory disease. It has been shown that high doses of ionizing radiation, as used in radiotherapy, can increase the risk of development or progression of atherosclerosis. To elucidate the effects of radiation on atherosclerosis, we propose a mathematical model to describe radiation-promoted plaque development. This model distinguishes itself from other models by combining plaque initiation and plaque growth, and by incorporating information from biological experiments. It is based on two consecutive processes: a probabilistic dose-dependent plaque initiation process, followed by deterministic plaque growth. As a proof of principle, experimental plaque size data from carotid arteries from irradiated ApoE mice was used to illustrate how this model can provide insight into the underlying biological processes. This analysis supports the promoting role for radiation in plaque initiation, but the model can easily be extended to include dose-related effects on plaque growth if available experimental data would point in that direction. Moreover, the model could assist in designing future biological experiments on this research topic. Additional biological data such as plaque size data from chronically-irradiated mice or experimental data sets with a larger variety in biological parameters can help to further unravel the influence of radiation on plaque development. To the authors’ knowledge, this is the first biophysical model that combines probabilistic and mechanistic modeling which uses experimental data to investigate the influence of radiation on plaque development.Electronic supplementary materialThe online version of this article (doi:10.1007/s00411-017-0709-2) contains supplementary material, which is available to authorized users.

Radiotherapy Is Associated with an Accelerated Risk of Ischemic Stroke in Oral Cavity Cancer Survivors after Primary Surgery

“…The radiation field for OCC is in the proximity of the carotid arteries, and the effect of ionizing radiation on plaque formation has been reported [10]. Despite the introduction of intensity-modulated RT in Taiwan, the late effects of radiation resulting in vascular injury are inevitable due to radiation scattering.…”

Accelerated Risk of Premature Ischemic Stroke in 5-Year Survivors of Nasopharyngeal Carcinoma

“…The effect of ionizing radiation on atherosclerosis has been previously reported . Radiation has a role in promoting plaque initiation and dose‐related effects on plaque growth . Despite the advent of intensity‐modulated radiotherapy , the late effects of radiation resulting in vascular injury are inevitable from the viewpoint of radiation scattering.…”

Dose rate effect on mortality from ischemic heart disease in the cohort of Russian Mayak Production Association workers

“…www.nature.com/scientificreports/ Experimental studies have shown both sparing and enhancing (inverse) dose protraction effects of radiation exposure on the circulatory system [23][24][25][26][27][28][29] , and consensus has not yet been reached regarding dose rate effectiveness 30,31 . Recently Kloosterman and colleagues 32 have developed a biophysical mathematical model to describe the radiation-promoted atheroslerotic plague development. The authors state that with the adequate experimental data available this model could be further elaborated to take into account the dose rate effect.…”