Characterization of cardiovascular injury in mice following partial-heart irradiation with clinically relevant dose and fractionation.
Characterization of cardiovascular injury in mice following partial-heart irradiation with clinically relevant dose and fractionation.
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DOI：
10.1016/j.radonc.2021.01.023
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Kirsch DG
中科院分区：
文献类型：
--
作者：
Lee CL;Lee JW;Daniel AR;Holbrook M;Hasapis S;Wright AO;Brownstein J;Da Silva Campos L;Ma Y;Mao L;Abraham D;Badea CT;Kirsch DG
晚期心脏毒性是乳腺癌放射治疗 (RT) 的主要副作用。我们开发并表征了辐射诱发心脏病的小鼠模型，该模型模拟左乳房和胸壁放疗的剂量、分割和射束排列。雌性野生型 (C57BL6/J) 和易患动脉粥样硬化的载脂蛋白 E 缺陷 (ApoE−/−) 小鼠（在 C57BL/6J 背景上）接受常规饮食，并通过左胸壁的相对切向光束接受 2 Gy × 25 部分的部分心脏照射。分别采用单光子发射计算机断层扫描（SPECT）和超声心动图检查C57BL/6J小鼠心肌灌注和心功能的变化。除了 SPECT 和超声心动图之外，还分别通过双能 microCT (DE-CT) 和压力-容积 (PV) 环分析检查 ApoE−/− 小鼠钙化斑块的形成和心脏功能的变化。通过组织病理学检查心肌纤维化的发展。与未受辐射的对照相比，受辐射的 C57BL/6J 小鼠在 2 Gy × 25 部分心脏辐射后长达 18 个月的 SPECT 或超声心动图显示没有显着变化，尽管受辐射的小鼠表现出心肌纤维化的适度增加。对于 ApoE−/− 小鼠，SPECT、DE-CT 或超声心动图显示 2 Gy × 25 部分心脏照射并未引起显着变化。然而，PV 环路分析显示，RT 后 12 个月，负荷依赖性收缩和舒张功能指标显着下降，包括心输出量、dV/dtmax 和 dV/dt min。对 C57BL/6J 和 ApoE−/− 小鼠进行临床相关剂量的部分心脏照射后，使用超声心动图、SPECT 和 DE-CT 等无创成像方式进行评估，没有发现与放疗相关的心肌灌注减少和心功能障碍的证据。然而，利用 PV 环分析进行的侵入性血流动力学评估表明，受辐射的 ApoE−/− 小鼠的心脏功能发生了微妙但显着的变化。 PV 环路分析可能对未来辐射诱发的心脏病的临床前研究有用，特别是如果预计心脏功能会发生微妙的变化。
Late cardiac toxicity is a major side effect of radiation therapy (RT) for breast cancer. We developed and characterized a mouse model of radiation-induced heart disease that mimics the dose, fractionation, and beam arrangement of left breast and chest wall RT. Female wild-type (C57BL6/J) and atherosclerosis-prone apolipoprotein E-deficient (ApoE−/−) mice (on a C57BL/6J background) on regular chow were treated with 2 Gy × 25 fractions of partial-heart irradiation via opposed tangential beams to the left chest wall. The changes in myocardial perfusion and cardiac function of C57BL/6J mice were examined by single-photon emission computed tomography (SPECT) and echocardiography, respectively. In addition to SPECT and echocardiography, the formation of calcified plaques and changes in cardiac function of ApoE−/− mice were examined by dual-energy microCT (DE-CT) and pressure-volume (PV) loop analysis, respectively. The development of myocardial fibrosis was examined by histopathology. Compared to unirradiated controls, irradiated C57BL/6J mice showed no significant changes by SPECT or echocardiography up to 18 months after 2 Gy × 25 partial-heart irradiation even though irradiated mice exhibited a modest increase in myocardial fibrosis. For ApoE−/− mice, 2 Gy × 25 partial-heart irradiation did not cause significant changes by SPECT, DE-CT, or echocardiography. However, PV loop analysis revealed a significant decrease in load-dependent systolic and diastolic function measures including cardiac output, dV/dtmax and dV/dt min 12 months after RT. Following clinically relevant doses of partial-heart irradiation in C57BL/6J and ApoE−/− mice, assessment with noninvasive imaging modalities such as echocardiography, SPECT, and DE-CT yielded no evidence of decreased myocardial perfusion and cardiac dysfunction related to RT. However, invasive hemodynamic assessment with PV loop analysis indicated subtle, but significant, changes in cardiac function of irradiated ApoE−/− mice. PV loop analysis may be useful for future preclinical studies of radiation-induced heart disease, especially if subtle changes in cardiac function are expected.
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影响因子：
158.5
作者：
Darby, Sarah C.;Ewertz, Marianne;Hall, Per
通讯作者：
Hall, Per
DOI：
10.1161/01.atv.14.1.133
发表时间：
1994-01-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
NAKASHIMA, Y;PLUMP, AS;ROSS, R
通讯作者：
ROSS, R
影响因子：
11.2
作者：
Boerma, M;Wang, JR;Hauer-Jensen, M
通讯作者：
Hauer-Jensen, M
影响因子：
7.3
作者：
Lee CL;Moding EJ;Cuneo KC;Li Y;Sullivan JM;Mao L;Washington I;Jeffords LB;Rodrigues RC;Ma Y;Das S;Kontos CD;Kim Y;Rockman HA;Kirsch DG
通讯作者：
Kirsch DG
DOI：
10.1016/j.mrrev.2016.07.003
发表时间：
2016-10
期刊：
Mutation research. Reviews in mutation research
影响因子：
--
作者：
Boerma M;Sridharan V;Mao XW;Nelson GA;Cheema AK;Koturbash I;Singh SP;Tackett AJ;Hauer-Jensen M
通讯作者：
Hauer-Jensen M