Cardiovascular diseases related to ionizing radiation : the risk of low-dose exposure (Review)

Traditionally, non-cancer diseases are not considered as health risks following exposure to low doses of ionizing radiation. Indeed, non-cancer diseases are classified as deterministic tissue reactions, which are characterized by a threshold dose. It is judged that below an absorbed dose of 100 mGy, no clinically relevant tissue damage occurs, forming the basis for the current radiation protection system concerning non-cancer effects. Recent epidemiological findings point, however, to an excess risk of non-cancer diseases following exposure to lower doses of ionizing radiation than was previously thought. The evidence is the most sound for cardiovascular disease (CVD) and cataract. Due to limited statistical power, the dose-risk relationship is undetermined below 0.5 Gy; however, if this relationship proves to be without a threshold, it may have considerable impact on current low‑dose health risk estimates. In this review, we describe the CVD risk related to low doses of ionizing radiation, the clinical manifestation and the pathology of radiation-induced CVD, as well as the importance of the endothelium models in CVD research as a way forward to complement the epidemiological data with the underlying biological and molecular mechanisms

Differential response to acute low dose radiation in primary and immortalized endothelial cells

Purpose : The low dose radiation response of primary human umbilical vein endothelial cells (HUVEC) and its immortalized derivative, the EA.hy926 cell line, was evaluated and compared. Material and methods: DNA damage and repair, cell cycle progression, apoptosis and cellular morphology in HUVEC and EA.hy926 were evaluated after exposure to low (0.05-0.5 Gy) and high doses (2 and 5 Gy) of acute X-rays. Results : Subtle, but significant increases in DNA double-strand breaks (DSB) were observed in HUVEC and EA.hy926 30 min after low dose irradiation (0.05 Gy). Compared to high dose irradiation (2 Gy), relatively more DSB/Gy were formed after low dose irradiation. Also, we observed a dose-dependent increase in apoptotic cells, down to 0.5 Gy in HUVEC and 0.1 Gy in EA.hy926 cells. Furthermore, radiation induced significantly more apoptosis in EA.hy926 compared to HUVEC. Conclusions : We demonstrated for the first time that acute low doses of X-rays induce DNA damage and apoptosis in endothelial cells. Our results point to a non-linear dose-response relationship for DSB formation in endothelial cells. Furthermore, the observed difference in radiation-induced apoptosis points to a higher radiosensitivity of EA.hy926 compared to HUVEC, which should be taken into account when using these cells as models for studying the endothelium radiation response

Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation

Ionizing radiation can elicit harmful effects on the cardiovascular system at high doses. Endothelial cells are critical targets in radiation-induced cardiovascular damage. Astronauts performing a long-term deep space mission are exposed to consistently higher fluences of ionizing radiation that may accumulate to reach high effective doses. In addition, cosmic radiation contains high linear energy transfer (LET) radiation that is known to produce high values of relative biological effectiveness (RBE). The aim of this study was to broaden the understanding of the molecular response to high LET radiation by investigating the changes in gene expression in endothelial cells. For this purpose, a human endothelial cell line (EA.hy926) was irradiated with accelerated nickel ions (Ni) (LET, 183 keV/mu m) at doses of 0.5, 2 and 5 Gy. DNA damage was measured 2 and 24 h following irradiation by gamma-H2AX foci detection by fluorescence microscopy and gene expression changes were measured by microarrays at 8 and 24 h following irradiation. We found that exposure to accelerated nickel particles induced a persistent DNA damage response up to 24 h after treatment. This was accompanied by a downregulation in the expression of a multitude of genes involved in the regulation of the cell cycle and an upregulation in the expression of genes involved in cell cycle checkpoints. In addition, genes involved in DNA damage response, oxidative stress, apoptosis and cell-cell signaling (cytokines) were found to be upregulated. An in silico analysis of the involved genes suggested that the transcription factors, E2F and nuclear factor (NF)-kappa B, may be involved in these cellular responses

When I relive a positive me: Vivid autobiographical memories facilitate autonoetic brain activation and enhance mood

Autobiographical memory is vital for our well-being and therefore used in therapeutic interventions. However, not much is known about the (neural) processes by which reliving memories can have beneficial effects. This study investigates what brain activation patterns and memory characteristics facilitate the effectiveness of reliving positive autobiographical memories for mood and sense of self. Particularly, the role of vividness and autonoetic consciousness is studied. Participants (N= 47) with a wide range of trait self-esteem relived neutral and positive memories while their bold responses, experienced vividness of the memory, mood, and state self-esteem were recorded. More vivid memories related to better mood and activation in amygdala, hippocampus and insula,indicative of increased awareness of oneself (i.e., prereflective aspect of autonoetic con-sciousness). Lower vividness was associated with increased activation in the occipital lobe, PCC, and precuneus, indicative of a more distant mode of reliving. While individuals with lower trait self-esteem increased in state self-esteem, they showed less deacti-vation of the lateral occipital cortex during positive memories. In sum, the vividness of the memory seemingly distinguished a more immersed and more distant manner of memory reliving. In particular, when reliving positive memories higher vividness facilitated increased prereflective autonoetic consciousness, which likely is instrumental in boosting mood

Dental Pulp Stem Cell Recruitment Signals within Injured Dental Pulp Tissue

The recruitment of dental pulp stem cells (DPSC) is a prerequisite for the regeneration of dentin damaged by severe caries and/or mechanical injury. Understanding the complex process of DPSC recruitment will benefit future in situ tissue engineering applications based on the stimulation of endogenous DPSC for dentin pulp regeneration. The current known mobilization signals and subsequent migration of DPSC towards the lesion site, which is influenced by the pulp inflammatory state and the application of pulp capping materials, are reviewed. The research outcome of migration studies may be affected by the applied methodology, which should thus be chosen with care. Both the advantages and disadvantages of commonly used assays for investigating DPSC migration are discussed. This review highlights the fact that DPSC recruitment is dependent not only on the soluble chemotactic signals, but also on their interaction with neighboring cells and the extracellular matrix, which can be modified under pathological conditions. These are discussed to explain how these modifications lead to the stimulation of DPSC recruitment

Complement C3a Mobilizes Dental Pulp Stem Cells and Specifically Guides Pulp Fibroblast Recruitment

International audienceIntroduction: Complement activation is considered as a major mechanism in innate immunity. Although it is mainly involved in initiating inflammation, recent data reported its involvement in other processes such as tissue regeneration. In the dental pulp, Complement C5a fragment has been shown to be involved in the recruitment of dental pulp stem cells (DPSCs). This study sought to investigate the possible role of C3a, another complement fragment, in the early steps of dentin-pulp regeneration.Methods: Expression of C3a receptor (C3aR) was investigated by immunofluorescence and RT-PCR on cultured pulp fibroblasts, STRO-1-sorted DPSCs as well as on human tooth sections in vivo. The effect of C3a on proliferation of both DPSCs and pulp fibroblasts was investigated by MTT assay. Cell migration under a C3a gradient was investigated using microfluidic chemotaxis chambers.Results: C3aR was expressed in vivo as well as in cultured pulp fibroblasts co-expressing Fibroblast Surface Protein and in DPSCs co-expressing STRO-1. Addition of recombinant C3a induced a significant proliferation of both cell types. When subjected to a C3a gradient, DPSCs were mobilized but not specifically recruited, while pulp fibroblasts were specifically recruited following a C3a gradient.Conclusions: These results provide the first demonstration of C3aR expression in the dental pulp and demonstrate that C3a is involved in increasing DPSCs and fibroblast proliferation, in mobilizing DPSCs and in specifically guiding fibroblast recruitment. This provides an additional link to the tight correlation between inflammation and tissue regeneration

Light-cured Tricalcium Silicate Toxicity to the Dental Pulp

International audienceIntroduction: Numerous studies reported dentin bridge formation after pulp capping with tricalcium silicates. By contrast, pulp capping with resins leads to pulp toxicity and inflammation. Hybrid materials made up of tricalcium silicates and resins have also been developed to be used in direct pulp capping. This work was designed to study the consequences of adding resins to tricalcium silicates by investigating TheraCal (BISCO, Lançon De Provence, France) and Biodentine (Septodont, Saint Maur des Fosses, France) interactions with the dental pulp. Methods: Media conditioned with the biomaterials were used to analyze pulp fibroblast proliferation using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test and proinflammatory cytokine interleukin 8 (IL-8) secretion using the enzyme-linked immunosorbent assay. The effects of conditioned media on dentin sialoprotein (DSP) and nestin expression by dental pulp stem cells (DPSCs) were investigated by immunofluorescence. The materials' interactions with the vital pulp were investigated using the entire tooth culture model. Results: TheraCal-conditioned media significantly decreased pulp fibroblast proliferation, whereas no effect was observed with Biodentine. When DPSCs were cultured with Biodentine-conditioned media, immunofluorescence showed an increased expression of DSP and nestin. This expression was lower with TheraCal, which significantly induced proinflammatory IL-8 release both in cultured fibroblasts and entire tooth cultures. This IL-8 secretion increase was not observed with Biodentine. Entire tooth culture histology showed a higher mineralization with Biodentine, whereas significant tissue disorganization was observed with TheraCal. Conclusions: Within the limits of these preclinical results, resincontaining TheraCal cannot be recommended for direct pulp capping

Characterization and angiogenic potential of xenogeneic bone grafting materials: Role of periodontal ligament cells

International audienceAdequate revascularization is a prerequisite for successful healing of periodontal bone defects. This study characterized threedifferent xenogeneic bone grafting materials: Gen-Os of equine and porcine origins, and anorganic Bio-Oss. We also investigatedtheir angiogenic potential. All materials were composed of poorly crystalline calcium oxide phosphate, with Bio-Oss exhibiting acarbonated phase and larger particle size and both Gen-Os showing the presence of collagen. Both Gen-Os materials significantlyenhanced vascular endothelial growth factor (VEGF) secretion by PDL cells. A significant increase in endothelial cell proliferationwas observed in cultures with both Gen-Os conditioned media, but not with that of Bio-Oss. Finally, angiogenesis was stimulatedby both Gen-Os conditioned media as demonstrated by an increased formation of capillary-like structures. Taken together, thesefindings indicate an enhanced angiogenic potential of both Gen-Os bone grafting materials when applied on PDL cells, most likely byincreasing VEGF production