Abstract 11385: Oxidative Stress, a Mediator of Human Saphenous Vein Bypass Graft Dysfunction
BACKGROUND: Surgical revascularization using greater saphenous vein (GSV) remains standard therapy for patients with atherosclerotic coronary and peripheral artery disease. Unfortunately, outcomes remain limited by vein graft failure, the leading cause of which is intimal hyperplasia (IH). The pathogenesis of IH remains incompletely understood but is thought to evolve from vein graft injury. Oxidative stress is a well recognized phenomenon contributing to vascular dysfunction, but is not a recognized etiology of vein graft failure. HYPOTHESIS: We investigated the hypothesis that oxidative stress contributes to vein graft dysfunction.
METHODS: Unmanipulated (UM) GSV segments were collected from human subjects immediately after surgical removal. Additional paired GSV was collected after conventional surgical manipulation (AM), which included hydrostatic distention and marking for orientation. GSV rings were suspended in a muscle bath. Force measurements were obtained after administration of phenylephrine (PE) and carbachol (CCH). Superoxide radical production was measured in UM and AM GSV by assessing conversion of dihydroethidium to superoxide-specific product 2-hydroxyethidium using high-performance liquid chromatography. Mass spectroscopy was performed to assess post-translational protein modifications.
RESULTS: Mean endothelial-dependent relaxation to CCH was 20.1% in UM-GSV versus -0.7% in AM-GSV (n=35, p>0.0001). Mean smooth muscle contractile response to PE was 0.068 N/m2 in UM-GSV versus 0.037 N/m2 in AM-GSV (n=40, p>0.0001). Surgical stress-induced injury significantly increased oxidative stress as measured by superoxide of 412 pmol/mg protein in AM-GSV compared to 262 in UM-GSV (n=4, p=0.03). Proteomics analysis of UM and AM-GSV demonstrated differential phosphorylation of proteins SSB, HSP27, and HSP90, all of which are involved in antioxidant defense.
CONCLUSIONS: Surgical vein graft preparation induces oxidative stress and differential phosphorylation of proteins involved in antioxidant defense. This correlates with endothelial dysfunction and impaired smooth muscle responses. These data argue for therapeutic interventions to reduce oxidative stress during vein graft preparation.
- © 2012 by American Heart Association, Inc.