0080: Dietary acrylamide induces accelerated endothelial aging in murine and human cell model

Abstract

Replicative senescence is characterized by a limited ability of cells to divide in-vitro . Senescence induces an endothelial dysfunction. Many compounds in food can induce an earlier vascular senescence. Acrylamide (AAM) is a recent discovery in food, as a Maillard reaction product. After ingestion, AAM is in part metabolized to glycidamide (GA) in the liver. AAM and GA have been described as “probably carcinogenic to human”, reprotoxic and neurotoxic in animals. However, endothelial toxicity of AAM has never been studied. To assess the effects of AAM on endothelium. To evaluate endothelial dysfunction, mice have been fed with AAM-enriched diets (25, 50 or 100μg/kgBW/day) for 3, 6 or 9 months. Endothelium-dependent relaxation (EDR) of aortic rings was measured. AAM (1-50mM) and GA (1-5mM) toxicity was assessed by measuring Human Umbilical Vein Endothelial Cells (HUVEC) proliferation by MTS test and cell death induction by flow cytometry. Senescence was evaluated in HUVEC cultured over 3 months with AAM or GA (10 or 100μm) by measuring β-galactosidase activity (flow cytometry) and telomere length (qPCR). After 6 months of diet, AAM (100[μg/kgBW/day) decreased aortic EDR (p<0.01). In-vitro , AAM (≥5 mm) inhibited in dose- and time-dependent manners HUVEC proliferation (p<0.001) and induced apoptosis (p<0.05). GA exhibited higher toxicity since lower doses were needed to induce same results. The extended culture with AAM or GA demonstrated a significant cell division slowdown and increased β-galactosidase activity.AAM or GA (100μm) accelerated telomere shortening (p<0.05). The toxicity of AAM and GA on endothelial cells in vitro is characterized by decreased proliferation and induction of cell death at high doses. Chronic exposure at lower concentrations induce an accelerated senescence, potentially the cause of endothelial dysfunction in-vivo .