| Autor: |
Mathias D; Department of Radiation Therapy, University of Leipzig, Leipzig, Germany., Mitchel RE; Radiological Protection Research and Instrumentation Branch, Canadian Nuclear Laboratories, Chalk River, Ontario, Canada., Barclay M; Departments of Pathology and Laboratory Medicine and Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; Vascular Biology Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada., Wyatt H; Radiological Protection Research and Instrumentation Branch, Canadian Nuclear Laboratories, Chalk River, Ontario, Canada., Bugden M; Radiological Protection Research and Instrumentation Branch, Canadian Nuclear Laboratories, Chalk River, Ontario, Canada., Priest ND; Radiological Protection Research and Instrumentation Branch, Canadian Nuclear Laboratories, Chalk River, Ontario, Canada., Whitman SC; Departments of Pathology and Laboratory Medicine and Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; Vascular Biology Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada., Scholz M; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany., Hildebrandt G; Department of Radiotherapy and Radiation Oncology, University of Rostock, Rostock, Germany., Kamprad M; Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig, Leipzig, Germany., Glasow A; Department of Radiation Therapy, University of Leipzig, Leipzig, Germany. |
| Abstrakt: |
Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025-0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025-2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05-2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and intervention of radiation related, long-term side effects but also give important implications for low dose anti-inflammatory radiotherapy. |
