10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model.

10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model.
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DOI:
10.3109/09553000903264473
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发表时间:
2009-12
影响因子:
2.6
通讯作者:
Moulder JE
Moulder JE
中科院分区:
医学3区
文献类型:
--
作者:
Baker JE;Fish BL;Su J;Haworth ST;Strande JL;Komorowski RA;Migrino RQ;Doppalapudi A;Harmann L;Allen Li X;Hopewell JW;Moulder JE

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确定10戈伊全身照射(TBI)或局部胸部照射(与放射性恐怖威胁相关的剂量)对脂质和肝脏特征、冠状动脉微血管和心室功能的影响。WAG/RijCmcr大鼠接受10戈伊TBI后进行骨髓移植或10戈伊局部胸部照射。与之匹配的未受辐射的大鼠作为对照。比较血脂和肝酶,冠状动脉血管形态,一氧化氮合酶(NOS)亚型,蛋白酶激活受体(PAR)-1表达和纤维蛋白原水平。二维应变超声心动图评估心脏的整体径向和周向应变。TBI导致总胆固醇和低密度脂蛋白(LDL)胆固醇持续升高(分别为190±8 vs. 58±6; 82±8 vs. 13±3 mg/dL)。冠状小动脉密度降低32%。组织学显示一些血管完全堵塞,而心肌细胞保持正常。TBI导致细胞动脉周围纤维化,而对照心脏具有对称的穿透血管,胶原蛋白和成纤维细胞较少。TBI 120天后,内皮型NOS和诱导型NOS蛋白分别下降32±4%和28±3%,纤维蛋白原和PAR-1蛋白分别升高21±4%和35±5%。与对照组相比,TBI降低了径向应变(19±8 vs. 46±7%)和周向应变(-8 3 vs. −15±3%)。仅胸部照射在相同的时间范围内没有产生变化。10戈伊的TBI(与放射性恐怖威胁相关的剂量)使血脂水平恶化,冠状动脉微血管受损,内皮生理学和心肌力学改变。这些变化在胸部局部照射时不明显。非胸部循环因素可能会促进辐射引起的心脏损伤。
To determine the impact of 10 Gy total body irradiation (TBI) or local thorax irradiation, a dose relevant to a radiological terrorist threat, on lipid and liver profile, coronary microvasculature and ventricular function. WAG/RijCmcr rats received 10 Gy TBI followed by bone marrow transplantation, or 10 Gy local thorax irradiation. Age-matched, non-irradiated rats served as controls. The lipid profile and liver enzymes, coronary vessel morphology, nitric oxide synthase (NOS) isoforms, protease activated receptor (PAR)-1 expression and fibrinogen levels were compared. Two dimensional strain echocardiography assessed global radial and circumferential strain on the heart. TBI resulted in a sustained increase in total and low density lipoprotein (LDL) cholesterol (190±8 vs. 58±6; 82±8 vs. 13±3 mg/dL, respectively). The density of small coronary arterioles was decreased by 32%. Histology revealed complete blockage of some vessels while cardiomyocytes remained normal. TBI resulted in cellular peri-arterial fibrosis whereas control hearts had symmetrical penetrating vessels with less collagen and fibroblasts. TBI resulted in a 32±4% and 28±3% decrease in endothelial NOS and inducible NOS protein respectively, and a 21±4% and 35±5% increase in fibrinogen and PAR-1 protein respectively, after 120 days. TBI reduced radial strain (19±8 vs. 46±7%) and circumferential strain (-8±3 vs. −15±3%) compared to controls. Thorax-only irradiation produced no changes over the same time frame. TBI with 10 Gy, a dose relevant to radiological terrorist threats, worsened lipid profile, injured coronary microvasculature, altered endothelial physiology and myocardial mechanics. These changes were not manifest with local thorax irradiation. Non-thoracic circulating factors may be promoting radiation-induced injury to the heart.
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发表时间: 1999-04-01
影响因子: 2.6
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发表时间: 2008-01-01
影响因子: 10.8
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发表时间: 2003-06-01
期刊: Radiation Research
影响因子: 3.4
作者:
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