Reduction of Atherosclerotic Lesions by the Chemotherapeutic Agent Carmustine Associated to Lipid Nanoparticles
Reduction of Atherosclerotic Lesions by the Chemotherapeutic Agent Carmustine Associated to Lipid Nanoparticles
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DOI：
10.1007/s10557-016-6675-0
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发表时间：
2016-10-01
影响因子：
3.4
通讯作者：
Maranhao, Raul C.
中科院分区：
文献类型：
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作者：
Daminelli, Elaine N.;Martinelli, Ana E. M.;Maranhao, Raul C.
在注射到血流中后，类似于低密度脂蛋白（LDL）的脂质纳米颗粒（LDE）集中在胆固醇喂养的兔的动脉粥样硬化病变中。在这里，动脉粥样硬化的兔子用卡莫司汀治疗，卡莫司汀是一种用于癌症化疗的抗增殖剂，与LDE结合，以研究对病变的影响。4周后，9只动物用静脉内盐水溶液处理，9只动物用单独的静脉内LDE处理，9只动物用静脉内LDE-卡莫司汀处理（4 mg/kg，每周一次，持续4周）dDE-卡莫司汀与对照相比使病变尺寸减小90%。LDE-卡莫司汀减少了动脉内膜中巨噬细胞、血管平滑肌细胞和调节性T细胞的存在，以及基质金属肽酶-9、白细胞介素-1 β和TNF-α和脂蛋白受体（即LDL受体、LDL相关蛋白-1、清道夫受体B类成员1）的存在。当单独注射时，LDE与注射的生理盐水溶液没有差异，LDE-卡莫司汀治疗导致病变面积、巨噬细胞和血管平滑肌细胞以及促炎因子对动脉内膜的侵袭显著减少。因此，这种新的制剂显示出治疗动脉粥样硬化性心血管疾病的巨大潜力。
After injection in the bloodstream, a lipid nanoparticle (LDE) resembling low-density lipoprotein (LDL) concentrates in atherosclerotic lesions of cholesterol-fed rabbits. Here, rabbits with atherosclerosis were treated with carmustine, an antiproliferative agent used in cancer chemotherapy, associated to LDE to investigate the effects on the lesions.Twenty-seven male New Zealand rabbits were fed a 1 % cholesterol diet for 8 weeks. After 4 weeks nine animals were treated with intravenous saline solution, nine with intravenous LDE alone, and nine with intravenous LDE-carmustine (4 mg/kg, weekly for 4 weeks).LDE-carmustine reduced lesion size by 90 % compared to the controls. LDE-carmustine reduced the presence of macrophages, vascular smooth muscle cells, and regulatory T cells in the arterial intima, as well as the presence of matrix metallopeptidase-9, interleukin-1 beta and TNF-alpha and lipoprotein receptors, namely LDL-receptor, LDL-related protein-1, scavenger receptor class B member 1. When injected alone, without association to carmustine, LDE was not different from injected saline solution.LDE-carmustine treatment resulted in marked reduction of lesion area, of the invasion of the arterial intima by macrophages and vascular smooth muscle cells and pro-inflammatory factors. Therefore, this new formulation shows great potential for therapy of atherosclerotic cardiovascular disease.