Little Mark P, Gola Anna, Tzoulaki Ioanna
Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom.
PLoS Comput Biol. 2009 Oct;5(10):e1000539. doi: 10.1371/journal.pcbi.1000539. Epub 2009 Oct 23.
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.
动脉粥样硬化是冠心病和中风的主要病因，而这两种疾病是发达社会中两大主要死因。越来越多的证据表明，在接受每日低剂量辐射的各类职业暴露人群中，低辐射剂量会增加心血管疾病风险。假设这些关联具有因果关系，那么慢性分次辐射暴露对心血管疾病产生影响的机制尚不清楚。我们概述了一个动脉粥样硬化的空间反应扩散模型，并尽可能基于人体数据进行稳定性分析。我们发现，多次小剂量辐射的一个预测结果是，平均趋化因子（MCP - 1）浓度会随累积剂量呈线性增加。MCP - 1增加的主要驱动因素是单核细胞死亡以及随之而来的MCP - 1降解减少。该模型预测的辐射诱发风险在数量上与一些职业暴露人群中观察到的风险一致。平衡态MCP - 1浓度随低密度脂蛋白胆固醇浓度的变化也与实验和流行病学数据相符。这种提出的机制可以通过实验进行验证。如果属实，它对放射防护也具有重要意义，因为目前放射防护并未考虑心血管疾病。日本原子弹幸存者的数据表明，心血管疾病和癌症死亡率对辐射诱发风险的贡献相似。评估心血管疾病低剂量风险的主要不确定性在于剂量反应关系的形状，这在日本的数据中并不明确。本文的分析表明，对于这个终点，线性外推法是合适的。
