The uptake and distribution of phosphorothioate oligonucleotides into vascular smooth muscle cells in vitro and in rabbit arteries.

The uptake and distribution of phosphorothioate oligonucleotides into vascular smooth muscle cells in vitro and in rabbit arteries.
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体外和兔动脉中血管平滑肌细胞对硫代磷酸寡核苷酸的摄取和分布。

DOI:
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发表时间:
1995
期刊:
Antisense Research and Development
影响因子:
--
通讯作者:
T. Burgess
T. Burgess
中科院分区:
--
文献类型:
--
作者:
C. Farrell;J. Bready;S. Kaufman;Y. Qian;T. Burgess

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Oligonucleotides are a class of compounds with potential as therapeutics for a variety of clinical applications. Local delivery of oligonucleotides to the arterial wall is a challenging aspect of the development of these therapeutics for restenosis, and herein we report experiments characterizing the uptake and distribution of phosphorothiate oligonucleotides into vascular smooth muscle cells in primary cultures and in rabbit arteries. Primary cultures of smooth muscle cells incubated with rhodamine-oligonucleotides showed uptake only into cytoplasmic vesicles. No nuclear or cytosolic localization was detected. In normal arteries there was no visible tissue or cellular uptake of oligonucleotides after intralumenal administration. However, in balloon-injured arteries there was significant oligonucleotide uptake into the tissue with apparent cytoplasmic delivery to the medial smooth muscle cells, as evinced by intense staining of their nuclei with labeled oligonucleotides. Measurement of FITC-oligonucleotide in artery extracts showed significantly greater uptake in injured, compared with normal arteries. Light and electron microscopic studies demonstrated a correlation between the degree of damage and the amount of uptake. These results demonstrate that oligonucleotides penetrate easily into the arterial wall of balloon-injured arteries and accumulate in the medial smooth muscle cells-the target cells for antirestenosis therapeutics following balloon angioplasty.
注射的寡脱氧核糖核苷酸快速核积累。
DOI: --
发表时间: 1990
期刊: The New biologist
影响因子: --
作者:
Chin,DJ;Green,GA;Zon,G;SzokaJr,FC;Straubinger,RM
通讯作者: Straubinger,RM
DOI: 10.1089/ard.1994.4.67
发表时间: 1994
期刊: Antisense research and development
影响因子: --
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Stein,CA;Krieg,AM
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DOI: 10.1161/01.cir.88.3.1215
发表时间: 1993
期刊: Circulation
影响因子: 37.8
作者:
Rogers,C;Karnovsky,MJ;Edelman,ER
通讯作者: Edelman,ER
DOI: 10.1161/01.cir.88.3.1190
发表时间: 1993
期刊: Circulation
影响因子: 37.8
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Shi,Y;Hutchinson,HG;Hall,DJ;Zalewski,A
通讯作者: Zalewski,A
DOI: --
发表时间: 1992
期刊: The American journal of pathology
影响因子: --
作者:
Olson,NE;Chao,S;Lindner,V;Reidy,MA
通讯作者: Reidy,MA