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Neuropeptide Y (NPY): A neurogenic mediator of angiogenesis
Visa övriga samt affilieringar
2004 (Engelska)Ingår i: 7th International NPY Meeting Coimbra, 2004, s. 36-36Konferensbidrag, Publicerat paper (Övrigt vetenskapligt)
Abstract [en]

NPY, previously known as a sympathetic vasoconstricting co-transmitter, recently has also emerged as an important vascular growth factor, stimulating proliferation of vascular smooth muscle and endothelial cells (ECs). Both in vitro and in vivo, NPY stimulates angiogenesis starting at sub-picomolar, non-vasoconstrictive concentrations, and with maximal effects similar to those of other known angiogenic factors e.g. vascular endothelial growth factor (VEGF). To determine if NPY is a physiological mediator in vivo, we studied 1 ) ischemic angiogenesis in a rodent model of femoral artery occlusion 2) vascular development in rats over-expressing NPY gene; 3) changes in angiogenesis with aging. Hindlimb ischemia increased local NPY release and shifted NPY receptor (R) expression from predominantly Yl to the Y2R type, and up-regulated dipeptidyl peptidase IV (DPPIV, peptidase forming Y2/YS agonist). Increasing local NPY levels 2-fold with a slow-release pellet (Il.g/14 days, below arterial occlusion), additionally induced YSR mRNA, and stimulated capillary angiogenesis and collateral vessel growth - leading to restoration of blood flow and contractile function of ischemic muscles. These effects were markedly reduced in Y2R-/- mice, as was NPY-induced aortic sprouting ex vivo; the latter was also reduced by anti-VEGF antibody and completely abolished in endothelial nitric oxide synthase (eNOS)-/- mice. The role of NPY in vascular development was further revealed by the severe impairment of spontaneous aortic sprouting in NPY-/- mice and changes in vascular density of non-ischemic muscles: reduction in Y2-/- mice and marked increase in NPY-Tg rats. With aging, in mice, NPY-induced angiogenesis decreased together with Y2 and DPPIV expression, and in human ECs, the proliferative effects of NPY declined too, similarly to those of VEGF or basic fibroblast growth factor (bFGF). Since NPY-induced EC proliferation was similarly blocked by anti-VEGF and anti-FGF antibodies in young and old patients, this suggests that age-induced impaired activity of the NPY-Y2R system could lead to lower secretion of these growth factors, in addition to decreased responsiveness of old vessels to VEGF and bFGF. Taken together, our studies indicate that NPY is a physiological neurogenic factor playing an important role ip revascularization of ischemic tissues and in age-related changes in vascular development. NPY's angiogenic activity requires Y2Rs and eNOS, and involves release of VEGF and bFGF. Thus, sympathetic nerve activity, via NPY, may be an important upstream mechanism triggering a cascade of molecular events leading to vascular remodeling during tissue ischemia and growth.

Ort, förlag, år, upplaga, sidor
2004. s. 36-36
Identifikatorer
URN: urn:nbn:se:hig:diva-2851OAI: oai:DiVA.org:hig-2851DiVA, id: diva2:119513
Konferens
7th International NPY Meeting Coimbra, Portugal, February 3-7, 2004
Tillgänglig från: 2007-11-05 Skapad: 2007-11-05 Senast uppdaterad: 2012-02-20Bibliografiskt granskad

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Totalt: 37 träffar
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