Periodic vs constant high glucose in inducing pro-inflammatory cytokine expression in human coronary artery endothelial cells

Abstract

Fluctuating hyperglycemia exerts a more deleterious effect than constant hyperglycemia on cardiovascular outcome in diabetic patients. We investigated the inflammatory responses of human coronary artery endothelial cells (HCAECs) to constant and periodic high glucose in vitro. HCAECs were incubated for 72 h continuously either in normal glucose (5.5 mmol/L), constant high glucose (25 mmol/L glucose), periodic high glucose (5.5 and 25 mmol/L glucose alternating every 6 h) or mannitol. Concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-α and intercellular adhesion molecule (ICAM)-1 in the supernatants of cell culture were measured using ELISA kits. The mRNAs of IL-6, TNF-α and ICAM-1 were evaluated by real-time quantitative PCR. Periodic high glucose caused a more intense inflammatory response than normal glucose and constant high glucose in HCAECs, with a marked increase in IL-6, TNF-α and ICAM-1 in supernatants of cell culture (P < 0.05). The concentrations of the three pro-inflammatory cytokine mRNAs were higher in cells exposed to periodic high glucose than those exposed to constant high glucose and normal glucose (P < 0.05). In cultured HCAECs, periodic high glucose evoked a more intense inflammatory response than constant high glucose.