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转录共激活因子 PCAF 的下调抑制血管平滑肌细胞的增殖和迁移,并减弱 NF-κB 介导的炎症反应。

Downregulation of the transcriptional co-activator PCAF inhibits the proliferation and migration of vascular smooth muscle cells and attenuates NF-κB-mediated inflammatory responses.

机构信息

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.

出版信息

Biochem Biophys Res Commun. 2019 May 21;513(1):41-48. doi: 10.1016/j.bbrc.2019.03.157. Epub 2019 Mar 29.

Abstract

P300/CBP-associated factor (PCAF) regulates vascular inflammation. This study was to explore the effect of PCAF on the proliferation and migrationof vascular smooth muscle cells (VSMCs) and neointimal hyperplasia in balloon-injured rat carotid artery. Downregulation of PCAF remarkably suppressed VSMCs proliferation and migration induced by lipopolysaccharide, and also significantly inhibit the nuclear translocation of nuclear factor-kappaB p65. Meanwhile, downregulation of PCAF inhibited the mRNA expression of tumor necrosis factor-α and interleukin-6, and also the levels in culture supernatants. Moreover, downregulation of PCAF profoundly reduced the intima area and the ratio of intima area to media area in balloon-injured rat carotid artery. In addition, the expression of PCNA and NF-κB p65 in intima were decreased by downregulation of PCAF. These results highlight that PCAF may be a potential target for prevention and treatment of neointimal hyperplasia and restenosis after angioplasty.

摘要

P300/CBP 相关因子(PCAF)调节血管炎症。本研究旨在探讨 PCAF 对血管平滑肌细胞(VSMCs)增殖和迁移以及球囊损伤大鼠颈总动脉内膜增生的影响。下调 PCAF 可显著抑制脂多糖诱导的 VSMCs 增殖和迁移,并显著抑制核因子-κB p65 的核转位。同时,下调 PCAF 抑制肿瘤坏死因子-α和白细胞介素-6 的 mRNA 表达及其在培养上清液中的水平。此外,下调 PCAF 可显著减少球囊损伤大鼠颈总动脉内膜面积和内膜面积与中膜面积的比值。此外,下调 PCAF 可降低内膜中 PCNA 和 NF-κB p65 的表达。这些结果表明,PCAF 可能是预防和治疗血管成形术后再狭窄和内膜增生的潜在靶点。

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