Abstract 499: Increased Lysine Acetylation After ‘Back-table’ Preparation of Human Saphenous Vein

Abstract

BACKGROUND Back-table preparation of human saphenous vein (SV) for surgical bypass results in conduit injury. We hypothesized that surgical manipulation results in increased total lysine acetylation, a global marker of injury. We examined effect of injury on acetylation of NFkB, a transcription factor involved in vascular smooth muscle proliferation. METHODS Paired SV samples were collected prior to surgical manipulation (UM) and after distention and marking (AM). SV rings were suspended in a muscle bath for measurement of contractile force in response to KCl and phenylephrine (PE); endothelial-dependent relaxation in response to carbachol (CCh); and endothelial-independent relaxation in response to sodium nitroprusside (SNP). Western blot analysis was used to measure total lysine and NFkB acetylation, results were normalized to GAPDH. RESULTS AM-SV generated significantly reduced physiologic parameters compared with UM-SV, including response to KCl (0.05 vs. 0.14 N/m 2 , n=9, p<0.05), PE (0.04 vs. 0.08 N/m 2 , n=7, p<0.05), endothelial-dependent relaxation (3.8% vs. 17.2%, n=7, p<0.05), and endothelial-independent relaxation (25.1% vs. 52.9%, n=7, p<0.05). Total lysine acetylation was increased in AM-SV compared to UM-SV (Fig1A), as was acetylation of NFkB (Fig1B). CONCLUSIONS Surgical preparation of SV results in physiologic dysfunction, and leads to increase in total lysine and NFkB acetylation. Increases in total lysine acetylation may be a global marker of injury and are associated with senescence. Increased acetylation of NFkB may correlate with the uncontrolled proliferative response of intimal the hyperplastic lesions.