Influence of mast cells on structural and functional manifestations of radiation-induced heart disease
Influence of mast cells on structural and functional manifestations of radiation-induced heart disease
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DOI：
10.1158/0008-5472.can-04-4333
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发表时间：
2005-04-15
期刊：
影响因子：
11.2
通讯作者：
Hauer-Jensen, M
中科院分区：
文献类型：
--
作者：
Boerma, M;Wang, JR;Hauer-Jensen, M
放射诱发的心脏病（RIHD）以加速动脉粥样硬化和不良组织重塑为特征，是胸部和胸壁肿瘤放疗后的严重后遗症。 RIHD 和其他心脏疾病中的不良心脏重塑经常伴有肥大细胞增生，表明肥大细胞可能影响心脏纤维化的发展。本研究使用肥大细胞缺陷大鼠模型来确定肥大细胞在 RIHD 中的作用。肥大细胞缺陷大鼠 (Ws/Ws) 和具有肥大细胞活性的同窝对照 (+/+) 接受 18 Gy 局部单剂量心脏照射。照射后六个月，通过超声心动图和兰根多夫灌注离体心脏制备检查心脏功能，同时使用定量组织学和免疫组织化学分析评估结构变化。肥大细胞缺陷的大鼠比肥大细胞健全的同窝大鼠表现出更严重的辐射后变化。因此，肥大细胞缺陷大鼠的左心室（IV）舒张压-容积关系表现出更大的向上/向左移动（P = 0.001），体内IV舒张面积更大程度减少（从年龄匹配对照组的0.50+/-0.024cm到照射后的0.24+/-0.032cm；P=0.006），并且IV后壁厚度更大程度增加。 （从年龄匹配对照中的 0.13 +/- 0.003 减少到照射后的 0.15 +/- 0.003 厘米；P = 0.04）。结构分析显示，肥大细胞缺陷大鼠的心脏中，放射后间质胶原 III 的积累更加明显，但心肌变性较少。这些数据表明，肥大细胞的缺乏加速了受辐射心脏功能变化的发展，特别是舒张功能障碍，并且表明，与普遍的假设相反，肥大细胞在 RIHD 中的作用主要是保护性的。
Radiation-induced heart disease (RIHD), characterized by accelerated atherosclerosis and adverse tissue remodeling, is a serious sequelae after radiotherapy of thoracic and chest wall tumors. Adverse cardiac remodeling in RIHD and other cardiac disorders is frequently accompanied by mast cell hyperplasia, suggesting that mast cells may affect the development of cardiac fibrosis. This study used a mast cell-deficient rat model to define the role of mast cells in RIHD. Mast cell-deficient rats (Ws/Ws) and mast cell-competent littermate controls (+/+) were exposed to 18 Gy localized single-dose irradiation of the heart. Six months after irradiation, cardiac function was examined by echocardiography and Langendorff-perfused isolated heart preparation, whereas structural changes were assessed using quantitative histology and immunohistochemical analysis. Mast cell-deficient rats exhibited more severe postradiation changes than mast cell-competent littermates. Hence, mast cell-deficient rats exhibited a greater upward/leftward shift in the left ventricular (IV) diastolic pressure-volume relationship (P = 0.001), a greater reduction in in vivo IV diastolic area (from 0.50 +/- 0.024 cm in age-matched controls to 0.24 +/- 0.032 cm after irradiation; P = 0.006), and a greater increase in IV posterior wall thickness (from 0.13 +/- 0.003 cut in age-matched controls to 0.15 +/- 0.003 cm after irradiation; P = 0.04). Structural analysis revealed more pronounced postradiation accumulation of interstitial collagen III but less myocardial degeneration in hearts from mast cell-deficient rats. These data show that the absence of mast cells accelerates the development of functional changes in the irradiated heart, particularly diastolic dysfunction, and suggest that, in contrast to what has been the prevailing assumption, the role of mast cells in RIHD is predominantly protective.