神经肽 Y 缺乏可减轻小鼠血管损伤后的新生内膜形成。

Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice.

机构信息

Department of Cardiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Group of Neuroendocrinology, Garvan Institute of Medical Research, 384 Victoria St, Sydney, Australia.

出版信息

BMC Cardiovasc Disord. 2023 May 6;23(1):239. doi: 10.1186/s12872-023-03267-y.

DOI:10.1186/s12872-023-03267-y

PMID:37149580

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10164319/

Abstract

BACKGROUND

Restenosis after percutaneous coronary intervention (PCI) limits therapeutic revascularization. Neuropeptide Y (NPY), co-stored and co-released with the sympathetic nervous system, is involved in this process, but its exact role and underlying mechanisms remain to be fully understood. This study aimed to investigate the role of NPY in neointima formation after vascular injury.

METHODS

Using the left carotid arteries of wild-type (WT, NPY-intact) and NPY-deficient (NPY) mice, ferric chloride-mediated carotid artery injury induced neointima formation. Three weeks after injury, the left injured carotid artery and contralateral uninjured carotid artery were collected for histological analysis and immunohistochemical staining. RT-qPCR was used to detect the mRNA expression of several key inflammatory markers and cell adhesion molecules in vascular samples. Raw264.7 cells were treated with NPY, lipopolysaccharide (LPS), and lipopolysaccharide-free, respectively, and RT-qPCR was used to detect the expression of these inflammatory mediators.

RESULTS

Compared with WT mice, NPY mice had significantly reduced neointimal formation three weeks after injury. Mechanistically, immunohistochemical analysis showed there were fewer macrophages and more vascular smooth muscle cells in the neointima of NPY mice. Moreover, the mRNA expression of key inflammatory markers such as interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and intercellular adhesion molecule-1 (ICAM-1) was significantly lower in the injured carotid arteries of NPY mice, compared to that in the injured carotid arteries of WT mice. In RAW264.7 macrophages, NPY significantly promoted TGF-β1 mRNA expression under unactivated but not LPS-stimulated condition.

CONCLUSIONS

Deletion of NPY attenuated neointima formation after artery injury, at least partly, through reducing the local inflammatory response, suggesting that NPY pathway may provide new insights into the mechanism of restenosis.

摘要

背景

经皮冠状动脉介入治疗（PCI）后的再狭窄限制了治疗性血运重建。神经肽 Y（NPY）与交感神经系统共存并共同释放，参与这一过程，但确切作用和潜在机制仍有待充分了解。本研究旨在探讨 NPY 在血管损伤后新生内膜形成中的作用。

方法

使用野生型（WT，NPY 完整）和 NPY 缺陷型（NPY）小鼠的左颈动脉，采用三氯化铁介导的颈动脉损伤诱导新生内膜形成。损伤 3 周后，采集左损伤颈动脉和对侧未损伤颈动脉进行组织学分析和免疫组织化学染色。采用 RT-qPCR 检测血管样本中几种关键炎症标志物和细胞黏附分子的 mRNA 表达。分别用 NPY、脂多糖（LPS）和无 LPS 的 Raw264.7 细胞处理，采用 RT-qPCR 检测这些炎症介质的表达。

结果

与 WT 小鼠相比，NPY 小鼠在损伤后 3 周时新生内膜形成明显减少。机制上，免疫组织化学分析显示 NPY 小鼠新生内膜中的巨噬细胞较少，血管平滑肌细胞较多。此外，与 WT 小鼠损伤颈动脉相比，NPY 小鼠损伤颈动脉中关键炎症标志物如白细胞介素 6（IL-6）、转化生长因子-β1（TGF-β1）和细胞间黏附分子-1（ICAM-1）的 mRNA 表达明显降低。在 RAW264.7 巨噬细胞中，NPY 在未激活但非 LPS 刺激条件下显著促进 TGF-β1 mRNA 表达。