Department of Radiation Oncology, School of Medicine, Klinikum rechts der Isar, Technische Universität München (TUM), Munich, Germany.
Center for Translational Cancer Research (TranslaTUM), School of Medicine Radiation Immuno-Oncology Group, Klinikum rechts der Isar, Technische Universität München (TUM), Ismaningerstr. 22, 81675, Munich, Germany.
Strahlenther Onkol. 2023 Dec;199(12):1214-1224. doi: 10.1007/s00066-023-02130-5. Epub 2023 Sep 2.
Radiotherapy is a major pillar in the treatment of solid tumors including breast cancer. However, epidemiological studies have revealed an increase in cardiac diseases approximately a decade after exposure of the thorax to ionizing irradiation, which might be related to vascular inflammation. Therefore, chronic inflammatory effects were examined in primary heart and lung endothelial cells (ECs) of mice after local heart irradiation.
Long-lasting effects on primary ECs of the heart and lung were studied 20-50 weeks after local irradiation of the heart of mice (8 and 16 Gy) in vivo by multiparameter flow cytometry using antibodies directed against cell surface markers related to proliferation, stemness, lipid metabolism, and inflammation, and compared to those induced by occlusion of the left anterior descending coronary artery.
In vivo irradiation of the complete heart caused long-lasting persistent upregulation of inflammatory (HCAM, ICAM‑1, VCAM-1), proliferation (CD105), and lipid (CD36) markers on primary heart ECs and an upregulation of ICAM‑1 and VCAM‑1 on primary ECs of the partially irradiated lung lobe. An artificially induced heart infarction induces similar effects with respect to inflammatory markers, albeit in a shorter time period.
The long-lasting upregulation of prominent inflammatory markers on primary heart and lung ECs suggests that local heart irradiation induces chronic inflammation in the microvasculature of the heart and partially irradiated lung that leads to cardiac injury which might be related to altered lipid metabolism in the heart.
放射疗法是治疗实体肿瘤（包括乳腺癌）的主要手段之一。然而，流行病学研究表明，在胸部接受电离辐射照射约十年后，心脏病的发病率会增加，这可能与血管炎症有关。因此，本研究旨在观察小鼠心脏局部照射后原发性心脏和肺内皮细胞（EC）中的慢性炎症反应。
通过多参数流式细胞术，使用针对与增殖、干性、脂质代谢和炎症相关的细胞表面标志物的抗体，研究了 20-50 周后局部心脏照射（8 和 16Gy）对小鼠心脏原发性 EC 的长期影响，并将其与左前降支冠状动脉阻塞引起的影响进行了比较。
心脏的全范围照射会导致原发性心脏 EC 上的炎症标志物（HCAM、ICAM-1、VCAM-1）、增殖标志物（CD105）和脂质标志物（CD36）的持续上调，并且会导致部分照射的肺叶的原发性 EC 上的 ICAM-1 和 VCAM-1 上调。人工诱导的心肌梗死在炎症标志物方面也会产生类似的影响，但时间较短。
原发性心脏和肺 EC 上主要炎症标志物的长期上调表明，心脏局部照射会导致心脏和部分照射肺的微血管慢性炎症，从而导致心脏损伤，这可能与心脏脂质代谢的改变有关。
