Losartan treatment attenuates tumor-induced myocardial dysfunction.
Losartan treatment attenuates tumor-induced myocardial dysfunction.
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DOI：
10.1016/j.yjmcc.2015.05.007
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发表时间：
2015-08
影响因子：
5
通讯作者：
Wold LE
中科院分区：
文献类型：
--
作者：
Stevens SC;Velten M;Youtz DJ;Clark Y;Jing R;Reiser PJ;Bicer S;Devine RD;McCarthy DO;Wold LE
疲劳和肌肉萎缩是癌症患者的常见症状。来自动物模型的数据表明，血管紧张素参与肿瘤诱导的肌肉萎缩，并且肿瘤生长可以独立地影响心肌功能，这可能导致癌症患者的疲劳。在临床研究中，血管紧张素转换酶（ACE）抑制剂可以防止化疗引起的心血管功能障碍的发展，提示肾素-血管紧张素-醛固酮系统（RAAS）的机制作用。在本研究中，我们研究血管紧张素（AT）1受体拮抗剂是否可以防止肿瘤相关的心肌功能障碍的发展。方法和结果：将Colon 26腺癌（c26）细胞植入8周龄的雌性CD 2F 1小鼠中。同时，小鼠每天通过饮水给予氯沙坦（10 mg/kg）。在体内超声心动图，血压，体外心肌细胞功能，细胞增殖试验，全身炎症和心肌蛋白降解的措施进行了19天后，肿瘤细胞注射。洛沙坦治疗可防止肿瘤诱导的肌肉质量损失和体外c26细胞增殖，降低肿瘤重量，并减弱心肌白细胞介素-6的表达。此外，氯沙坦治疗减轻了心肌细胞中钙信号的肿瘤相关改变，这与荷瘤小鼠心脏中心肌细胞收缩速度、收缩功能和血压的改善有关。结论：氯沙坦可减轻肿瘤引起的心肌功能障碍和炎症反应。
Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin-angiotensin-aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT)1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. Methods and Results: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8 weeks of age. Simultaneously, mice were administered Losartan (10 mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19 days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. Conclusions: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation.