Key result
Low dose cardiac irradiation (0.2 Gy) induced premature death in 47% of ApoE-/- mice at 20 weeks (p=0.0019) and caused significant left ventricular dysfunction and early pro-inflammatory macrophage polarization.
Why the study?
Does low dose ionizing radiation induce long-term cardiac remodeling and interact with atherosclerosis in ApoE-/- and wild-type mice?
Does low dose ionizing radiation induce long-term cardiac remodeling and interact with atherosclerosis in ApoE-/- and wild-type mice?
p-value: p=0.0019
Atherosclerotic predisposition exacerbates cardiac damage from low-dose ionizing radiation, driven by early pro-inflammatory macrophage polarization.
Suggests heightened cardiac vulnerability to low-dose radiation in atherosclerosis; leaves open human translation from murine models.
AIM: Investigating long-term cardiac effects of low doses of ionizing radiation is highly relevant in the context of interventional cardiology and radiotherapy. Epidemiological data report that low doses of irradiation to the heart can result in significant increase in the cardiovascular mortality by yet unknown mechanisms. In addition co-morbidity factor such as hypertension or/and atherosclerosis can enhance cardiac complications. Therefore, we explored the mechanisms that lead to long-term cardiac remodelling and investigated the interaction of radiation-induced damage to heart and cardiovascular systems with atherosclerosis, using wild-type and ApoE-deficient mice. METHODS AND RESULTS: ApoE-/- and wild-type mice were locally irradiated to the heart at 0, 0.2 and 2 Gy (RX). Twenty, 40 and 60 weeks post-irradiation, echocardiography were performed and hearts were collected for cardiomyocyte isolation, histopathological analysis, study of inflammatory infiltration and fibrosis deposition. Common and strain-specific pathogenic pathways were found. Significant alteration of left ventricular function (eccentric hypertrophy) occurred in both strains of mice. Low dose irradiation (0.2 Gy) induced premature death in ApoE-/- mice (47% died at 20 weeks). Acute inflammatory infiltrate was observed in scarring areas with accumulation of M1-macrophages and secretion of IL-6. Increased expression of the fibrogenic factors (TGF-β1 and PAI-1) was measured earlier in cardiomyocytes isolated from ApoE-/- than in wt animals. CONCLUSION: The present study shows that cardiac exposure to low dose of ionizing radiation induce significant physiological, histopathological, cellular and molecular alterations in irradiated heart with mild functional impairment. Atherosclerotic predisposition precipitated cardiac damage induced by low doses with an early pro-inflammatory polarization of macrophages.
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Monceau et al. (2013) studied Radiation-induced cardiac disease (n=153). Low dose ionizing radiation vs. Sham-irradiated (0 Gy) was evaluated on Survival and cardiac physiological parameters (p=0.0019). Low dose cardiac irradiation (0.2 Gy) induced premature death in 47% of ApoE-/- mice at 20 weeks (p=0.0019) and caused significant left ventricular dysfunction and early pro-inflammatory macrophage polarization.
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