Neuropeptide Y-induced acceleration of postangioplasty occlusion of rat carotid artery
Neuropeptide Y-induced acceleration of postangioplasty occlusion of rat carotid artery
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DOI：
10.1161/01.atv.0000071349.30914.25
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发表时间：
2003-07-01
影响因子：
8.7
通讯作者：
Zukowska, Z
中科院分区：
文献类型：
--
作者：
Li, LJ;Lee, EW;Zukowska, Z
目的-尝试通过血管成形术恢复动脉粥样硬化血管的血流通常会导致再狭窄。由于神经在此过程中的作用尚不清楚，因此我们研究了具有血管有丝分裂活性的交感神经递质 Y (NPY) 是否有助于血管成形术后再狭窄。方法和结果-颈动脉球囊血管成形术在 6 至 24 小时内上调了 NPY 及其加工酶 (DPPIV/cd26) 和受体 (Y1、Y2、Y5 mRNA 和蛋白质) 的血管表达，并且14天后刺激新内膜形成和血小板中NPY的积累。插入受伤动脉旁边的 NPY 颗粒（1 至 10 杯/颗粒，持续 14 天）可将血小板和血管 NPY 免疫反应性升高至应激样水平，并剂量依赖性增强血管成形术诱导的新内膜。引人注目的是，10 杯 NPY 持续 14 天导致血管闭塞，出现动脉粥样硬化样病变，并出现血栓和含有新血管、巨噬细胞、基质和脂质的新内膜。 Y1或Y5受体拮抗剂完全阻止了NPY的作用，并将血管成形术引起的新内膜减少了50%。结论-血管成形术上调了血小板和血管NPY系统，然后通过Y1和Y5受体激活促进新内膜形成。将 NPY 增加到高应激水平会引发血栓性动脉粥样硬化样病变和血管闭塞的形成。因此，NPY可能是加速动脉粥样硬化的危险因素，而NPY受体拮抗剂可能是治疗再狭窄的一种可能的新疗法。
Objective-Attempts to restore blood flow through atherosclerotic vessels by angioplasty often result in restenosis. Because the role of nerves in this process is unclear, we investigated whether neuropeptide Y (NPY), a sympathetic cotransmitter with vascular mitogenic activities, contributes to postangioplasty restenosis.Methods and Results-Carotid artery balloon angioplasty upregulated vascular expression of NPY and its processing enzyme (DPPIV/cd26) and receptors (Y1, Y2, Y5 mRNA and protein) within 6 to 24 hours and stimulated neointima formation and accumulation of NPY in platelets after 14 days. NPY pellets (1 to 10 mug/pellet for 14 days) inserted next to the injured artery elevated platelet and vascular NPY immunoreactivity to stress-like levels and dose-dependently augmented angioplasty-induced neointima. Strikingly, 10 mug NPY for 14 days led to vessel occlusion with an atherosclerotic-like lesion, with thrombus and neointima containing neovessels, macrophages, matrix, and lipids. Y1 or Y5 receptor antagonist completely prevented the effect of NPY and reduced angioplasty-induced neointima by 50%.Conclusions-Angioplasty upregulates platelet and vascular NPY systems, which then contribute to neointima formation via Y1 and Y5 receptor activation. Increasing NPY to high stress levels triggers formation of a thrombotic atherosclerotic-like lesion and vessel occlusion. Thus, NPY may be a risk factor for accelerated atherosclerosis, and NPY receptor antagonists may be a possible new treatment for restenosis.