High salt diet suppresses the angiogenic competency of bone marrow derived mononuclear cells

Abstract

Bone marrow derived mononuclear cell (BM‐MC) injection is a potential therapy for inducing revascularization in ischemic tissues, however more research is needed into how different disease states affect BM‐MC function. Previously, we have shown skeletal muscle angiogenesis induced by electrical stimulation (ES) is impaired in high salt diet (HSD) fed Sprague Dawley (SD) rats. In this study we tested the hypothesis that injection of BM‐MCs could normalize the microvessel density in HSD fed rats during ES. Following one week on HSD (4% NaCl), 7–8 week old SD rats received 8 hours per day of ES to their right hind limb for 7 days. One day prior to the onset of stimulation, vehicle or BM‐MCs derived from SD donor rats on HSD or normal salt (NSD) were injected intramuscularly into the stimulated limb or intravenously into the tail vein. Microvessel density in muscles of the stimulated limb, relative to the unstimulated limb, was significantly higher in rats injected with BM‐MCs from a NSD donor as compared to vehicle and BM‐MCs from HSD treated rats. We also determined by flow cytometry that a sub‐set of BM‐MCs that were CD34+ and VEGFR2+ were significantly suppressed in the HSD fed rats. This study suggests that HSD impairs the competency of BM‐MC to augment angiogenesis in skeletal muscle following ES and this may be due to a suppression of CD34+/VEGFR2+ cells in the bone marrow.