Abstract 5807: Psychological Stress Impairs Ischemia-induced Neovascularization

Abstract

Background: Psychological stress (PS) is a major risk factor for cardiovascular diseases but the underlying mechanisms are still largely unknown. Here we tested the hypothesis that PS might decrease neovascularization in response to ischemia. Methods and results: Balb/c mice were subjected to restraint stress by placing them in a well ventilated 50 mL conical centrifuge tube for 20 min each day for 14 days. Control mice were left unperturbed in their home cage with free access to food and water. After two weeks of this stress protocol, hindlimb ischemia was surgically provoked by femoral artery removal and hindlimb perfusion was then evaluated by Laser Doppler. Mice exposed to PS showed a significantly lower rate of blood flow recovery compared to control mice at day 14 (0.60±0.04 vs 0.78±0.05, p<0.05) and day 21 (0.61±0.07 vs 0.80±0.07, p<0.05) and had a significantly lower capillary density in ischemic muscles (38±1 vs 74±3 capillaries/mm 2 , p<0.001), as assessed by CD31 immunostaining. Endothelial progenitor cells (EPCs) have been shown to have an important role for postnatal neovascularization. We found that the number of peripheral EPCs was significantly decreased in PS mice compared to control mice and that EPCs from PS mice showed a significant impairment of their angiogenic activities (adhesion, migration, integration into tubules). Moreover, oxidative stress levels in EPCs isolated from mice exposed to PS were significantly increased as determined by DCF-DA and DHE immunostainings. Conclusions: PS is associated with a reduced neovascularization following ischemia. The potential mechanisms involved include increased oxidative stress, decreased EPCs number and impairment of their functional activities.