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Neuropeptide Y: a novel angiogenic factor from the sympathetic nerves and endothelium.
- Source :
-
Circulation research [Circ Res] 1998 Jul 27; Vol. 83 (2), pp. 187-95. - Publication Year :
- 1998
-
Abstract
- 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 Tyr1-Pro2 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.
- Subjects :
- Animals
Aorta drug effects
Capillaries
Collagen pharmacology
Dipeptidyl Peptidase 4 biosynthesis
Dipeptidyl Peptidase 4 genetics
Dipeptidyl Peptidase 4 physiology
Drug Combinations
Endothelial Growth Factors pharmacology
Female
Fibroblast Growth Factor 2 pharmacology
Gene Expression
Humans
Laminin pharmacology
Lymphokines pharmacology
Male
Mice
Mice, Inbred C57BL
Neuropeptide Y biosynthesis
Neuropeptide Y genetics
Neuropeptide Y isolation & purification
Neuropeptide Y metabolism
Neuropeptide Y pharmacology
Peptide Fragments metabolism
Peptide Fragments pharmacology
Polymerase Chain Reaction
Proteoglycans pharmacology
RNA, Messenger biosynthesis
Rats
Rats, Sprague-Dawley
Receptors, Neuropeptide Y biosynthesis
Receptors, Neuropeptide Y drug effects
Receptors, Neuropeptide Y genetics
Receptors, Neuropeptide Y physiology
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Endothelium, Vascular chemistry
Neovascularization, Physiologic drug effects
Neuropeptide Y physiology
Sympathetic Nervous System chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0009-7330
- Volume :
- 83
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 9686758
- Full Text :
- https://doi.org/10.1161/01.res.83.2.187