ANTISENSE OLIGONUCLEOTIDES TO THE P65 SUBUNIT OF NF-KB INHIBIT HUMAN VASCULAR SMOOTH-MUSCLE CELL ADHERENCE AND PROLIFERATION AND PREVENT NEOINTIMA FORMATION IN RAT CAROTID ARTERIES
ANTISENSE OLIGONUCLEOTIDES TO THE P65 SUBUNIT OF NF-KB INHIBIT HUMAN VASCULAR SMOOTH-MUSCLE CELL ADHERENCE AND PROLIFERATION AND PREVENT NEOINTIMA FORMATION IN RAT CAROTID ARTERIES
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DOI：
10.1006/bbrc.1995.2204
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发表时间：
1995-08-24
影响因子：
3.1
通讯作者：
OHLSTEIN, E
中科院分区：
文献类型：
--
作者：
AUTIERI, MV;YUE, TL;OHLSTEIN, E
与血管再狭窄相关的新内膜形成是一个复杂的局部炎症过程，积极涉及动脉粥样硬化病变的主要细胞成分血管平滑肌细胞。NF-kB是一种多种基因的多营养反激活因子，其激活与细胞对炎症的反应密切相关。我们用NF-kB的p65亚基上的磷酸化反义寡核苷酸处理人血管平滑肌细胞（VSMC），并报道了p65反义寡核苷酸（1-20 μ M）的添加，但不带意义或p50，以浓度依赖性的方式抑制人血管平滑肌细胞的粘附和增殖。此外，给药p65反义显著抑制球囊血管成成术大鼠颈动脉新生内膜的形成，表明NF-kB的p65亚基可激活在VSMC病理生物学中重要表达的基因。这些结果表明，去除p65可以通过抑制平滑肌细胞的增殖和粘附来减少新内膜的形成。(C) 1995学术出版社，Inc。
Neointima formation associated with vascular restenosis is a complex local inflammatory process actively involving the major cellular component of the atherosclerotic lesion, the vascular smooth muscle cell. NF-kB is a pleotrophic transactivator of a diverse group of genes whose activation has been strongly associated with the cellular response to inflammation. We treated human vascular smooth muscle cells (VSMC) with phosphorothio antisense oligonucleotides to the p65 subunit of NF-kB and report that addition of p65 antisense oligonucleotides (1-20 mu M), but not sense or p50, inhibit human VSMC adherence and proliferation in a concentration-dependent manner. Additionally, administration of p65 antisense significantly inhibited neointima formation in balloon angioplasty treated rat carotid arteries, indicating that the p65 subunit of NF-kB transactivates genes whose expression is important in VSMC pathobiology. These results suggest that abrogation of p65 reduces neointima formation by inhibition of smooth muscle cell proliferation and adherence. (C) 1995 Academic Press, Inc.