Neuropeptide Y - A novel angiogenic factor from the sympathetic nerves and endothelium
Neuropeptide Y - A novel angiogenic factor from the sympathetic nerves and endothelium
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DOI：
10.1161/01.res.83.2.187
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发表时间：
1998-07-27
影响因子：
20.1
通讯作者：
Grant, DS
中科院分区：
文献类型：
--
作者：
Zukowska-Grojec, Z;Karwatowska-Prokopczuk, E;Grant, DS
长期以来，交感神经一直被怀疑具有营养活性，但其血管生成因子的性质尚未确定。神经肽Y(NPY)是一种交感神经递质，是心脏和大脑中含量最丰富的多肽。它在神经激活和缺血时释放，引起血管收缩和平滑肌细胞增殖。在这里，我们报告了NPY是血管生成的第一个证据。在低生理浓度下，在体外，它促进血管的萌发和人内皮细胞的黏附、迁移、增殖和毛细血管的形成。在体内，在小鼠血管生成试验中，NPY是血管生成的，与碱性成纤维细胞生长因子一样有效。NPY的作用是特异的，由Y1和Y2受体介导。这两种受体的表达在细胞生长过程中上调；然而，Y2似乎是主要的NPY血管生成受体。它的上调类似于NPY诱导的重组基底膜(Matrigel)上毛细血管的形成；Y2激动剂模拟NPY的成管活性，而Y2拮抗剂则阻止它。内皮不仅含有NPY受体，还含有NPY自身、其mRNA和“NPY转换酶”二肽基肽酶IV(蛋白质和mRNA)，它终止NPY的Y1活性，并从NPY中裂解Tyr(1)-Pro(2)形成血管生成Y2激动剂。因此，NPY3-36内皮不仅是NPY的作用部位，也是自分泌NPY系统的起源，在组织的发育和修复过程中，NPY与交感神经一起可能在血管生成中起重要作用。
Sympathetic nerves have long been suspected of trophic activity, but the nature of their angiogenic factor has not been determined. Neuropeptide Y (NPY), a sympathetic cotransmitter, is the most abundant peptide in the heart and the brain. It is released during nerve activation and ischemia and causes vasoconstriction and smooth muscle cell proliferation. Here we report the first evidence that NPY is angiogenic. At low physiological concentrations, in vitro, it promotes vessel sprouting and adhesion, migration, proliferation, and capillary tube formation by human endothelial cells. In vivo, in a murine angiogenic assay, NPY is angiogenic and is as potent as a basic fibroblast growth factor. The NPY action is specific and is mediated by Y1 and Y2 receptors. The expression of both receptors is upregulated during cell growth; however, Y2 appears to be the main NPY angiogenic receptor. Its upregulation parallels the NPY-induced capillary tube formation on reconstituted basement membrane (Matrigel); the Y2 agonist mimics the tube-forming activity of NPY, whereas the Y2 antagonist blocks it. Endothelium contains not only NPY receptors but also peptide itself, its mRNA, and the "NPY-converting enzyme" dipeptidyl peptidase IV (both protein and mRNA), which terminates the Y1 activity of NPY and cleaves the Tyr(1)-Pro(2) from NPY to form an angiogenic Y2 agonist, NPY3-36 Endothelium is thus not only the site of action of NPY but also the origin of the autocrine NPY system, which, together with the sympathetic nerves, may be important in angiogenesis during tissue development and repair.