Neuropeptide Y - A novel angiogenic factor from the sympathetic nerves and endothelium

被引:329
作者
Zukowska-Grojec, Z
Karwatowska-Prokopczuk, E
Rose, W
Rone, J
Movafagh, S
Ji, H
Yeh, YY
Chen, WT
Kleinman, HK
Grouzmann, E
Grant, DS
机构
[1] Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA
[2] Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA
[3] Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA
[4] NIDR, Cell Biol Sect, Bethesda, MD 20892 USA
[5] Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA
[6] CHU Vaudois, Dept Hypertens, CH-1011 Lausanne, Switzerland
关键词
angiogenesis; chemotaxis; dipeptidyl peptidase IV; NPY; receptor; endothelial cell;
D O I
10.1161/01.RES.83.2.187
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:187 / 195
页数:9
相关论文
共 42 条
  • [1] CLONING AND FUNCTIONAL EXPRESSION OF A HUMAN Y4 SUBTYPE RECEPTOR FOR PANCREATIC-POLYPEPTIDE, NEUROPEPTIDE-Y, AND PEPTIDE YY
    BARD, JA
    WALKER, MW
    BRANCHEK, TA
    WEINSHANK, RL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (45) : 26762 - 26765
  • [2] EFFECT OF PLATELET FACTORS ON MIGRATION OF CULTURED BOVINE AORTIC ENDOTHELIAL AND SMOOTH-MUSCLE CELLS
    BELL, L
    MADRI, JA
    [J]. CIRCULATION RESEARCH, 1989, 65 (04) : 1057 - 1065
  • [3] GROWTH-STIMULATING EFFECT OF CATECHOLAMINES ON RAT AORTIC SMOOTH-MUSCLE CELLS IN CULTURE
    BLAES, N
    BOISSEL, JP
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 1983, 116 (02) : 167 - 172
  • [4] INTEGRATION OF FACTORS CONTROLLING VASCULAR TONE - OVERVIEW
    BURNSTOCK, G
    [J]. ANESTHESIOLOGY, 1993, 79 (06) : 1368 - 1380
  • [5] Molecular mechanisms of blood vessel formation
    Bussolino, F
    Mantovani, A
    Persico, G
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1997, 22 (07) : 251 - 256
  • [6] THALIDOMIDE IS AN INHIBITOR OF ANGIOGENESIS
    DAMATO, RJ
    LOUGHNAN, MS
    FLYNN, E
    FOLKMAN, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (09) : 4082 - 4085
  • [7] DELAFUENTE M, 1993, IMMUNOLOGY, V80, P259
  • [8] FRANCOCERECEDA A, 1990, CARDIOVASC RES, V24, P241
  • [9] A receptor subtype involved in neuropeptide-Y-induced food intake
    Gerald, C
    Walker, MW
    Criscione, L
    Gustafson, EL
    BatzlHartmann, C
    Smith, KE
    Vaysse, P
    Durkin, MM
    Laz, TM
    Linemeyer, DL
    Schaffhauser, AO
    Whitebread, S
    Hofbauer, KG
    Taber, RI
    Branchek, TA
    Weinshank, RL
    [J]. NATURE, 1996, 382 (6587) : 168 - 171
  • [10] INTERACTION OF ENDOTHELIAL-CELLS WITH A LAMININ-A CHAIN PEPTIDE (SIKVAV) INVITRO AND INDUCTION OF ANGIOGENIC BEHAVIOR INVIVO
    GRANT, DS
    KINSELLA, JL
    FRIDMAN, R
    AUERBACH, R
    PIASECKI, BA
    YAMADA, Y
    ZAIN, M
    KLEINMAN, HK
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 1992, 153 (03) : 614 - 625