HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tilan, J. U. Articles by Zukowska, Z. PubMed Articles by Tilan, J. U. Articles by Zukowska, Z.

Megakaryocyte/platelet-derived Neuropeptide Y (NPY), in addition to neuronal, is essential for ischemic revascularization in rodents

¹ Physiology & Biophysics, Georgetown University, Washington, DC
² Neurobiology, Garvan Institute of Medical Research, Sydney, Australia

ABSTRACT

Previously, we showed that sympathetically-derived NPY promotes ischemic revascularization after femoral artery occlusion (FAO) in rodents by activating Y2 receptors (Rs) and dipeptidyl peptidase IV (DPPIV), which forms a Y2/Y5-preferring agonist. The role of other NPY sources (platelets), Rs and temporal relationship to ischemic revascularization was unknown and is studied here. A critical role for NPY but not Y5R was shown in NPY^–/– and Y5^–/– mice whose post-FAO limb revascularization was markedly impaired and unchanged, respectively. Within 5 days, FAO in rats (expressing platelet NPY) elevated plasma NPY levels (neuronal) and Y1, Y2, DPPIV and NPY mRNA (vs. non-ischemic contralateral limb) in adductor (arteriogenesis zone) and gastrocnemius (angiogenesis zone) muscles; while density of CD31⁺-capillaries fell. Vascular density, CD31⁺- and smooth muscle -actin⁺-vessels, was restored by 14 days, when platelet levels doubled, and accelerated to 5 days by NPY slow-release pellet (below FAO, 1 µg/14 days). Platelet NPY and bone marrow NPY mRNA were increased after FAO in platelet NPY-expressing Sv129 WT mice, which were then used in a platelet depletion/transfer experiment [found (KA) to restore NPY atherosclerotic effects in resistant NPY^–/–] with NPY^–/–mice. Thus, early activation of neuronal and later activation of megakaryocyte/platelet-derived NPY is essential for ischemic revascularization. NIH grants HL067357 and HL055310 to Z.Z.

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tilan, J. U. Articles by Zukowska, Z. PubMed Articles by Tilan, J. U. Articles by Zukowska, Z.