The role of renin angiotensin system antagonists in the prevention of doxorubicin and trastuzumab induced cardiotoxicity.
The role of renin angiotensin system antagonists in the prevention of doxorubicin and trastuzumab induced cardiotoxicity.
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DOI：
10.1186/s12947-015-0011-x
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发表时间：
2015-04-03
影响因子：
1.9
通讯作者：
Jassal DS
中科院分区：
文献类型：
--
作者：
Akolkar G;Bhullar N;Bews H;Shaikh B;Premecz S;Bordun KA;Cheung DY;Goyal V;Sharma AK;Garber P;Singal PK;Jassal DS
肿瘤学是一门不断发展的学科，专注于治疗因治疗而发生心血管并发症的癌症患者的管理。尽管目前手术切除、放疗和化疗的组合可能导致癌症患者治愈，但抗癌药物，特别是阿霉素（DOX）和曲妥珠单抗（TRZ）的给药与心脏毒性风险增加相关。关于肾素-血管紧张素系统（RAS）拮抗剂在预防DOX+TRZ介导的心脏毒性中的潜在心脏保护作用知之甚少。本研究的目的是确定RAS拮抗剂是否可用于减弱DOX+TRZ诱导的心脏毒性。将总共240只C57 B1/6小鼠随机分配至安慰剂、阿利吉仑、培哚普利或缬沙坦的预防性治疗，总共13周。在每组中，小鼠接受DOX、TRZ或两种药物的组合治疗。每周进行一次连续的小鼠超声心动图检查，以表征各组内心血管重塑的程度。在用DOX+TRZ治疗的野生型（WT）小鼠中，LV舒张末期内径（LVID）从基线时的3.1 ± 0.2mm增加到第13周时的4.6 ± 0.3mm（p < 0.05），并且LV缩短分数（FS）从基线时的52 ± 2%降低到第13周时的26 ± 2%（p < 0.05）。阿利吉仑、培哚普利或缬沙坦预防性治疗减轻了LV腔扩张程度，第13周时LVID尺寸分别为3.9 ± 0.2 mm、4.1 ± 0.2 mm和4.2 ± 0.1 mm（p < 0.05）。类似地，用阿利吉仑、培哚普利或缬沙坦进行预防性治疗具有部分心脏保护作用，在第13周时FS分别为40 ± 1%、32 ± 1%和33 ± 2%（p < 0.05）。与接受DOX+TRZ的WT小鼠相比，RAS抑制的预防性治疗也与存活率改善相关，证实了超声心动图结果。在化疗诱导的心功能不全的慢性小鼠模型中，通过预防性给予RAS拮抗剂，DOX+TRZ的心脏毒性作用部分减弱。
Cardio-Oncology is an evolving discipline that focuses on the management of cancer patients who develop cardiovascular complications as a result of their treatment. Although the current combination of surgical resection, radiation, and chemotherapy may lead to a cure in cancer patients, the administration of anti-cancer drugs, in particular Doxorubicin (DOX) and Trastuzumab (TRZ), is associated with an increased risk of cardiotoxicity. Little is known on the potential cardioprotective role of renin angiotensin system (RAS) antagonists in the prevention of DOX+TRZ mediated cardiotoxicity. The aim of the study was to determine whether RAS antagonists would be useful in attenuating DOX+TRZ induced cardiotoxicity. A total of 240 C57Bl/6 mice were randomized to prophylactic treatment with placebo, Aliskiren, Perindopril, or Valsartan for a total of 13 weeks. Within each arm, mice received treatment with either DOX, TRZ, or the combination of both drugs. Serial murine echocardiography was performed weekly to characterize the degree of cardiovascular remodeling within each group. In wild-type (WT) mice treated with DOX+TRZ, LV end diastolic internal diameter (LVID) increased from 3.1 ± 0.2 mm at baseline to 4.6 ± 0.3 mm at week 13 (p < 0.05) and the LV fractional shortening (FS) decreased from 52 ± 2% at baseline to 26 ± 2% at week 13 (p < 0.05). Prophylactic treatment with Aliskiren, Perindopril, or Valsartan attenuated the degree of LV cavity dilatation with LVID dimensions of 3.9 ± 0.2 mm, 4.1 ± 0.2 mm, and 4.2 ± 0.1 mm at week 13, respectively (p < 0.05). Similarly, prophylactic treatment with Aliskiren, Perindopril, or Valsartan was partially cardioprotective with FS of 40 ± 1%, 32 ± 1%, and 33 ± 2% at week 13, respectively (p < 0.05). As compared to WT mice receiving DOX+TRZ, prophylactic treatment with RAS inhibition was also associated with improved survival, corroborating the echocardiographic findings. The cardiotoxic effects of DOX+TRZ were partially attenuated by the prophylactic administration of RAS antagonists in a chronic murine model of chemotherapy induced cardiac dysfunction.
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影响因子：
37.8
作者：
Nozaki, N;Shishido, T;Kubota, I
通讯作者：
Kubota, I
DOI：
10.1016/j.echo.2009.01.016
发表时间：
2009-04-01
影响因子：
6.5
作者：
Jassal, Davinder S.;Han, Song-Yee;Singal, Pawan K.
通讯作者：
Singal, Pawan K.
影响因子：
120.7
作者：
Gheorghiade, Mihai;Boehm, Michael;Maggioni, Aldo P.
通讯作者：
Maggioni, Aldo P.
影响因子：
3.8
作者：
Pituskin, Edith;Haykowsky, Mark;Paterson, Ian
通讯作者：
Paterson, Ian
影响因子：
3.2
作者：
Boucek, Robert J Jr;Steele, Ann;Atkinson, James
通讯作者：
Atkinson, James