Abstract
Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease at low radiation doses in various occupationally exposed groups receiving small daily radiation doses. Assuming that they are causal, the mechanisms for effects of chronic fractionated radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for atherosclerosis and perform stability analysis, based wherever possible on human data. We show that a predicted consequence of multiple small radiation doses is to cause mean chemo-attractant (MCP-1) concentration to increase linearly with cumulative dose. The main driver for the increase in MCP-1 is monocyte death, and consequent reduction in MCP-1 degradation. The radiation-induced risks predicted by the model are quantitatively consistent with those observed in a number of occupationally-exposed groups. The changes in equilibrium MCP-1 concentrations with low density lipoprotein cholesterol concentration are also consistent with experimental and epidemiologic data. This proposed mechanism would be experimentally testable. If true, it also has substantive implications for radiological protection, which at present does not take cardiovascular disease into account. The Japanese A-bomb survivor data implies that cardiovascular disease and cancer mortality contribute similarly to radiogenic risk. The major uncertainty in assessing the low-dose risk of cardiovascular disease is the shape of the dose response relationship, which is unclear in the Japanese data. The analysis of the present paper suggests that linear extrapolation would be appropriate for this endpoint.
Highlights
Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society [1]
We show that following multiple small radiation doses the chemo-attractant (MCP-1) concentration increases proportionally to cumulative dose; this is driven by radiation-induced monocyte death
This will result in risk of atherosclerosis increasing approximately linearly with cumulative dose
Summary
Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society [1]. There is emerging evidence of excess risk of cardiovascular disease at much lower radiation doses and occurring a long time after radiation exposure in the Japanese atomic bomb survivor Life Span Study (LSS) cohort [8,9] and in various occupationally-exposed groups [10,11,12,13,14] not in all (e.g., [15]). Assuming that they are causal, the likely mechanisms for such effects of low dose and/or chronic radiation exposures on cardiovascular disease are not clear [16,17]. There was dose-related elevation in erythrocyte sedimentation rate and in levels of IgG, IgA and total immunoglobulins in this cohort, all markers of systemic inflammation [19]
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