Citation: FASEB Journal. 27(6):2244-55, 2013 Jun..Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology.ISSN: 0892-6638.Full author list: Abe K; Burnett MS; Chalothorn D; Epstein SE; Everhart LM; Faber JE; Kitlinska J; Kuo-Bonde L; Tilan JU; Zukowska Z.UI/PMID: 23457218.Subject(s): *Blood Platelets/me [Metabolism] | *Ischemia/bl [Blood] | *Neovascularization, Physiologic | *Neuropeptide Y/ph [Physiology] | Animals | Cell Proliferation | Cells, Cultured | Disease Models, Animal | Endothelial Cells/pa [Pathology] | Hindlimb | Humans | Ischemia/ge [Genetics] | Ischemia/pp [Physiopathology] | Male | Mice | Mice, 129 Strain | Mice, Knockout | Neovascularization, Physiologic/ge [Genetics] | Neuropeptide Y/df [Deficiency] | Neuropeptide Y/ge [Genetics] | Rats | Rats, WistarInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal Article | Research Support, N.I.H., ExtramuralDigital Object Identifier: http://dx.doi.org/10.1096/fj.12-213546 (Click here)Abbreviated citation: FASEB J. 27(6):2244-55, 2013 Jun.Local Holdings: Available online from MWHC library: July 1987 - present (after 1 year).Abstract: We previously reported that the sympathetic neurotransmitter neuropeptide Y (NPY) is potently angiogenic, primarily through its Y2 receptor, and that endogenous NPY is crucial for capillary angiogenesis in rodent hindlimb ischemia. Here we sought to identify the source of NPY responsible for revascularization and its mechanisms of action. At d 3, NPY(-/-) mice demonstrated delayed recovery of blood flow and limb function, consistent with impaired collateral conductance, while ischemic capillary angiogenesis was reduced (~70%) at d 14. This biphasic temporal response was confirmed by 2 peaks of NPY activation in rats: a transient early increase in neuronally derived plasma NPY and increase in platelet NPY during late-phase recovery. Compared to NPY-null platelets, collagen-activated NPY-rich platelets were more mitogenic (~2-fold vs. ~1.6-fold increase) for human microvascular endothelial cells, and Y2/Y5 receptor antagonists ablated this difference in proliferation. In NPY(+/+) mice, ischemic angiogenesis was prevented by platelet depletion and then restored by transfusion of platelets from NPY(+/+) mice, but not NPY(-/-) mice. In thrombocytopenic NPY(-/-) mice, transfusion of wild-type platelets fully restored ischemia-induced angiogenesis. These findings suggest that neuronally derived NPY accelerates the early response to femoral artery ligation by promoting collateral conductance, while platelet-derived NPY is critical for sustained capillary angiogenesis.