Functionalized dendrimer-based delivery of angiotensin type 1 receptor siRNA for preserving cardiac function following infarction.
Functionalized dendrimer-based delivery of angiotensin type 1 receptor siRNA for preserving cardiac function following infarction.
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DOI：
10.1016/j.biomaterials.2013.02.008
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发表时间：
2013-05
期刊：
影响因子：
14
通讯作者：
Davis, Michael E.
中科院分区：
文献类型：
--
作者：
Liu, Jie;Gu, Catherine;Cabigas, E. Bernadette;Pendergrass, Karl D.;Brown, Milton E.;Luo, Ying;Davis, Michael E.
心血管疾病（CVD）是全世界死亡的主要原因，许多病理与炎症基因的上调有关。利用RNA干扰进行基因沉默是调控基因表达的有力工具，但由于缺乏有效的递送系统，其在心血管疾病中的应用一直受到阻碍。我们在此报道了在大鼠缺血再灌注（IR）模型中用于siRNA递送的蝌蚪树突材料的发展。血管紧张素II (Ang II) 1型受体（AT1R）是介导Ang II大部分不良反应的主要受体，被选为沉默靶点。在合成的三种蝌蚪树状大分子中，负载siRNA的低聚精氨酸共轭树状大分子在体外心肌细胞中表现出有效的下调AT1R表达。当树突材料在体内应用时，与生理盐水注射或空树突材料处理组相比，siRNA递送阻止了IR损伤后AT1R水平的增加，并显著改善了心功能恢复。这些实验证明了对IR损伤引起的功能障碍的潜在治疗方法，可能是AT1R阻断的替代方法。
Cardiovascular disease (CVD) is the leading cause of death throughout the world and much pathology is associated with upregulation of inflammatory genes. Gene silencing using RNA interference is a powerful tool in regulating gene expression, but its application in CVDs has been prevented by the lack of efficient delivery systems. We report here the development of tadpole dendrimeric materials for siRNA delivery in a rat ischemia-reperfusion (IR) model. Angiotensin II (Ang II) type 1 receptor (AT1R), the major receptor that mediates most adverse effects of Ang II, was chosen to be the silencing targeting. Among the three tadpole dendrimers synthesized, the oligo-arginine conjugated dendrimer loaded with siRNA demonstrated effective down-regulation in AT1R expression in cardiomyocytes in vitro. When the dendrimeric material was applied in vivo, the siRNA delivery prevented the increase in AT1R levels and significantly improved cardiac function recovery compared to saline injection or empty dendrimer treated groups after IR injury. These experiments demonstrate a potential treatment for dysfunction caused by IR injury and may represent an alternative to AT1R blockade.
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影响因子：
3.4
作者：
Gray WD;Che P;Brown M;Ning X;Murthy N;Davis ME
通讯作者：
Davis ME
影响因子：
3.7
作者：
Cigola, E;Kajstura, J;Anversa, P
通讯作者：
Anversa, P
影响因子：
4.8
作者：
DZAU, V;BRAUNWALD, E
通讯作者：
BRAUNWALD, E
DOI：
10.1177/107424840300800307
发表时间：
2003-09-01
影响因子：
2.6
作者：
Jugdutt, Bodh I.;Menon, Vijayan
通讯作者：
Menon, Vijayan
影响因子：
64.8
作者：
Eulalio, Ana;Mano, Miguel;Giacca, Mauro
通讯作者：
Giacca, Mauro