PEGylated-nanoliposomal clusterin for amyloidogenic light chain-induced endothelial dysfunction.
PEGylated-nanoliposomal clusterin for amyloidogenic light chain-induced endothelial dysfunction.
复制标题
DOI：
10.1080/08982104.2016.1274756
复制
发表时间：
2018-06
影响因子：
4.4
通讯作者：
Weissig V
中科院分区：
文献类型：
--
作者：
Guzman-Villanueva D;Migrino RQ;Truran S;Karamanova N;Franco DA;Burciu C;Senapati S;Nedelkov D;Hari P;Weissig V
轻链（AL）淀粉样变性是一种发病率和死亡率较高的疾病，由淀粉样轻链蛋白（LC）引发多器官损伤所致。目前尚无能够逆转LC毒性的治疗方法。我们之前的研究表明，伴侣糖蛋白簇集素（CLU）和纳米脂质体（NL）分别能够恢复被LC损害的人微血管内皮功能。在本研究中，我们旨在制备聚乙二醇化纳米脂质体簇集素（NL - CLU）制剂，该制剂既能综合发挥对抗LC的作用，又有可能有效地递送至微血管组织，并测试其对人小动脉内皮功能的疗效。NL - CLU是通过NL的羧基化表面与CLU蛋白的伯胺之间的偶联反应制备而成。NL由磷脂酰胆碱（PC）、胆固醇（Chol）和1,2 - 二硬脂酰 - sn - 甘油 - 3 - 磷酸乙醇胺 - N - [羧基（聚乙二醇） - 2000]（DSPE - PEG 2000羧酸）按70:25:5摩尔比制成。通过测量暴露于LC的人脂肪小动脉对乙酰胆碱和罂粟碱的舒张反应，来测试NL - CLU的保护作用。LC处理显著降低了对乙酰胆碱和罂粟碱的舒张反应；LC与聚乙二醇化纳米脂质体CLU或游离CLU共同处理则恢复了舒张反应。NL - CLU是一种可行且有前景的逆转LC诱导的内皮损伤的方法。
Light chain (AL) amyloidosis is a disease associated with significant morbidity and mortality arising from multi-organ injury induced by amyloidogenic light chain proteins (LC). There is no available treatment to reverse the toxicity of LC. We previously showed that chaperone glycoprotein clusterin (CLU) and nanoliposomes (NL), separately, restore human microvascular endothelial function impaired by LC. In this work, we aim to prepare PEGylated-nanoliposomal clusterin (NL-CLU) formulations that could allow combined benefit against LC while potentially enabling efficient delivery to microvascular tissue, and test efficacy on human arteriole endothelial function. NL-CLU was prepared by a conjugation reaction between the carboxylated surface of NL and the primary amines of the CLU protein. NL were made of phosphatidylcholine (PC), cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (DSPE-PEG 2000 carboxylic acid) at 70:25:5 mol%. The protective effect of NL-CLU was tested by measuring the dilation response to acetylcholine and papaverine in human adipose arterioles exposed to LC. LC treatment significantly reduced the dilation response to acetylcholine and papaverine; co-treatment of LC with PEGylated-nanoliposomal CLU or free CLU restored the dilator response. NL-CLU is a feasible and promising approach to reverse LC-induced endothelial damage.
登录
查看更多内容
PEG 对缀合葡萄球菌激酶的空间屏蔽效应的分子洞察：生化表征和分子动力学模拟
影响因子：
3.7
作者：
Mu Q;Hu T;Yu J
通讯作者：
Yu J
影响因子：
5.3
作者：
Franco, Daniel A.;Truran, Seth;Burciu, Camelia;Gutterman, David D.;Maltagliati, Anthony;Weissig, Volkmar;Hari, Parameswaran;Migrino, Raymond Q.
通讯作者：
Migrino, Raymond Q.
影响因子：
5.4
作者：
Franco DA;Truran S;Weissig V;Guzman-Villanueva D;Karamanova N;Senapati S;Burciu C;Ramirez-Alvarado M;Blancas-Mejia LM;Lindsay S;Hari P;Migrino RQ
通讯作者：
Migrino RQ
影响因子：
4.1
作者：
KIRBY, C;CLARKE, J;GREGORIADIS, G
通讯作者：
GREGORIADIS, G
影响因子：
4.8
作者：
Humphreys, DT;Carver, JA;Wilson, MR
通讯作者：
Wilson, MR