A Model of Cardiovascular Disease Giving a Plausible Mechanism for the Effect of Fractionated Low-Dose Ionizing Radiation Exposure

Little, Mark P.; Gola, Anna; Tzoulaki, Ioanna

doi:10.1371/journal.pcbi.1000539

Cited by 62 publications

(53 citation statements)

References 51 publications

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“…The somewhat high (albeit nonsignificant) risks for hypertensive heart disease and CeVD if RBM dose is used (Table 6) (weakly) suggest that dose to this tissue may not be relevant for these endpoints. There is biological data suggesting radiation-associated senescence of monocytes [39], and a some-what similar mechanism based on monocyte cell killing in the arterial intima suggests that the arterial intima may be causally associated with initiating atheroma in the arterial wall [40] (although there are many other stages between that point and plaque rupture [41,42]), so that mean arterial dose might be the most relevant organ or tissue dose for studying circulatory disease. Several recent reviews [8,9,28,43] describe the abundant radiobiological reasons for considering the studies of moderate and low doses separately from studies of high doses.…”

Section: Discussionmentioning

confidence: 99%

Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study

et al. 2015

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High-dose ionizing radiation is associated with circulatory disease. Risks from lower-dose fractionated exposures, such as from diagnostic radiation procedures, remain unclear. In this study we aimed to ascertain the relationship between fractionated low-to-medium dose radiation exposure and circulatory disease mortality in a cohort of 13,568 tuberculosis patients in Massachusetts, some with fluoroscopy screenings, between 1916 and 1961 and follow-up until the end of 2002. Analysis of mortality was in relation to cumulative thyroid (cerebrovascular) or lung (all other circulatory disease) radiation dose via Poisson regression. Over the full dose range, there was no overall radiation-related excess risk of death from circulatory disease (n = 3221; excess relative risk/Gy -0.023; 95 % CI -0.067, 0.028; p = 0.3574). Risk was somewhat elevated in hypertensive heart disease (n = 89; excess relative risk/Gy 0.357; 95 % CI -0.043, 1.030, p = 0.0907) and slightly decreased in ischemic heart dis-ease (n = 1950; excess relative risk/Gy -0.077; 95 % CI -0.130, -0.012; p = 0.0211). However, under 0.5 Gy, there was a borderline significant increasing trend for all circulatory disease (excess relative risk/Gy 0.345; 95 % CI -0.032, 0.764; p = 0.0743) and for ischemic heart disease (excess relative risk/Gy 0.465; 95 % CI, -0.032, 1.034, p = 0.0682). Pneumolobectomy increased radiation-associated risk (excess relative risk/Gy 0.252; 95 % CI 0.024, 0.579). Fractionation of dose did not modify excess risk. In summary, we found no evidence of radiation-associated excess circulatory death risk overall, but there are indications of excess circulatory death risk at lower doses (<0.5 Gy). Although consistent with other radiation-exposed groups, the indications of higher risk at lower doses are unusual and should be confirmed against other data.

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Section: Discussionmentioning

confidence: 99%

Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study

et al. 2015

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“…138 An examination of possible biological mechanisms indicates that the most likely target of radiation-induced cardiovascular damages are endothelial cells and subsequent induction of an inflammatory response. 144 Again, inflammation and, in general, non-targeted effects mediated by the microenvironment are the major pathways in radiation response of the organisms, 122 driving both cancer and non-cancer late effects, as well as for radiation therapy. 145 Generally speaking, the epidemiological evidence of non-cancer late effects in exposed individuals is consistent with radiationinduced acceleration of the ageing process.…”

Section: Late Effectsmentioning

confidence: 99%

New challenges in high-energy particle radiobiology

Durante

2014

BJR

125

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Densely ionizing radiation has always been a main topic in radiobiology. In fact, a-particles and neutrons are sources of radiation exposure for the general population and workers in nuclear power plants. More recently, high-energy protons and heavy ions attracted a large interest for two applications: hadrontherapy in oncology and space radiation protection in manned space missions. For many years, studies concentrated on measurements of the relative biological effectiveness (RBE) of the energetic particles for different end points, especially cell killing (for radiotherapy) and carcinogenesis (for late effects). Although more recently, it has been shown that densely ionizing radiation elicits signalling pathways quite distinct from those involved in the cell and tissue response to photons. The response of the microenvironment to charged particles is therefore under scrutiny, and both the damage in the target and non-target tissues are relevant. The role of individual susceptibility in therapy and risk is obviously a major topic in radiation research in general, and for ion radiobiology as well. Particle radiobiology is therefore now entering into a new phase, where beyond RBE, the tissue response is considered. These results may open new applications for both cancer therapy and protection in deep space.Biological effects of densely ionizing radiation have been studied since the beginning of radiobiology. As a matter of fact, a-particles deliver the main contribution to the background radiation dose on Earth, owing to inhalation of the indoor radon.1 Neutrons have also been extensively studied because of protection of workers in nuclear power plants; use of fast neutrons in radiotherapy; and of the exposure of the survivors of the atomic bomb in Hiroshima and Nagasaki, where a neutron component was added to g-rays. Bacq and Alexander 2 already elegantly described the radiobiology of a-particles and neutrons in their 1955 seminal book.More recently, radiobiology research has focused on highenergy protons and heavy ions, mostly for two reasons: charged particle therapy (CPT) in oncology and radiation protection in manned space missions. In both cases, charged particles at energies .100 MeV n 21 are involved. The characteristic depth-dose distribution with the sharp Bragg peak at the end of the range can be exploited for killing tumours; on the other hand, densely ionizing radiation can effectively delay tissue morbidity. Notwithstanding the many differences in exposure conditions, CPT and space radiation protection share several research topics, including individual sensitivity, non-targeted effects, late stochastic effects and so forth.3 Research in these fields requires large high-energy accelerators and is often performed by the same research groups with a common interest in particle radiobiology. Research is rapidly moving forward owing to the diffusion of CPT centres in the USA, Europe, and Asia 4 and to the growing interest in manned space exploration, now a priority for all space agencies, 5 but wi...

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“…Sensing the presence of the oxidized LDL (ox-LDL) in the intima, endothelial cells begin to secrete monocyte chemoattractant protein (MCP)-1 (Harrington 2000;Reape and Groot 1999), which attracts monocytes into the intima (Osterud and Bjorklid 2003). After entering the intima, monocytes differentiate into macrophages, which endocytose the ox-LDL (Gui et al 2012;Johnson and Newby 2009;Little et al 2009). The ingestion of large amounts of ox-LDL transforms the fatty macrophages into foam cells (Calvez et al 2009;Gui et al 2012).…”

Section: Introductionmentioning

confidence: 99%

A Mathematical Model of Atherosclerosis with Reverse Cholesterol Transport and Associated Risk Factors

Friedman

Hao

2014

Bull Math Biol

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Atherosclerosis, the leading cause of death in the US, is a disease in which a plaque builds up inside the arteries. The low density lipoprotein (LDL) and high density lipoprotein (HDL) concentrations in the blood are commonly used to predict the risk factor for plaque growth. In a recent paper (Hao and Friedman in Plos One e90497, 2014), we have developed a mathematical model of plaque growth which includes the (LDL, HDL) concentrations. In the present paper, we have refined that model by including the effect of reverse cholesterol transport. By exploration-by-examples of regression of a plaque in mice, our model simulations suggest that such drugs as used for mice may also slow plaque growth in humans. We next proceeded to explore the effects of oxidative stress or antioxidant deficiency, high blood pressure and cigarette smoking as risk factors. We suggest for an individual in one of these three risk categories and with specified (LDL, HDL) concentration, how to reduce or eliminate the risk of atherosclerosis.

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A Model of Cardiovascular Disease Giving a Plausible Mechanism for the Effect of Fractionated Low-Dose Ionizing Radiation Exposure

Cited by 62 publications

References 51 publications

Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study

Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study

New challenges in high-energy particle radiobiology

A Mathematical Model of Atherosclerosis with Reverse Cholesterol Transport and Associated Risk Factors

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