Platelet neuropeptide Y (NPY) and the collateral and capillary networks in skeletal muscle ischemia

Abstract

Previously, we showed that sympathetically‐derived or exogenous NPY promotes ischemic revascularization after femoral artery ligation (FAL) in rodents by activating Y2 receptors and dipeptidyl peptidase IV (DPPIV), which forms a Y2/Y5‐preferring agonist. FAL also induced early up‐regulation of Y2 and DPPIV mRNA in adductor (collateral zone, CZ) and gastrocnemius (capillary angiogenesis zone, AZ) muscles and elevated plasma NPY levels, followed by increased platelet NPY levels at 7 and 14 days post‐ligation. The latter findings suggested platelet NPY may play a role in angiogenesis/collateralization after FAL, which is evaluated in this study. In 129/SvlmJ/NPY+/+ mice, FAL induced an increase in capillary density (CD31+ vessels) in the AZ by 14 days (vs. sham), which in NPY‐/‐ remained unchanged (no difference in basal capillary density between NPY+/+ and NPY‐/‐ mice.). Transfer of NPY‐/‐ platelets into platelet‐depleted (Busulfan 25 mg/kg, i.p.) NPY+/+ mice attenuated the angiogenic response in the AZ, while NPY+/+ platelet transfer into NPY‐/‐ mice significantly increased the density of CD31+ vessels in this region. In a separate group of mice, adductor and plantar perfusion were decreased in NPY‐/‐ mice after FAL. These data suggest that NPY's effect on both the collateral and capillary networks promote ischemic revascularization and is, at least in part, mediated by platelet NPY.