Single Triglyceride-Rich Meal Destabilizes Barrier Functions and Initiates Inflammatory Processes of Endothelial Cells.

Abstract

Postprandial hypertriglyceridemia is an independent risk factor for cardiovascular disease. The aim of this study was to assess the effects of a single fat-rich meal on barrier functions and inflammatory status on human umbilical vascular endothelial cells (HUVECs), furthermore we assess the effects of mixture of palmitic acid and 25-hydroxycholesterol (PA +25OHCH) on integrity of endothelial cells and their inflammatory properties. HUVECs were induced with serum of healthy volunteers taken before, and 3 h after, the consumption of a meal with a standardized daily required dose of fats. In addition, endothelial cells were induced with PA +25OHCH (800 μM/L+10 μg/mL). Total cholesterol, triglycerides (TGs), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high sensitivity c-reactive protein, and glucose were measured at fasting and postprandially. HUVEC integrity was measured in the RTCA-DP xCELLigence system. mRNA expression of interleukin (IL)-33, IL-32, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), CX3C-chemokine, vascular endothelial growth factor (VEGF) occludin, and VE-cadherin was analyzed by real-time polymerase chain reaction. Viability and apoptosis were assessed in flow cytometry. The level of VEGF and IL-33 in fasting and postprandial serum was assessed by enzyme-linked immunosorbent assay (ELISA). Three hours after consumption of a fatty meal, all patients displayed increased levels of TGs and Toll-like receptors (110 ± 37 mg/dL versus 182 ± 64 mg/dL P < 0.05) (24 ± 11 mg/dL versus 42 ± 14 mg/dL P < 0.05). Postprandial serum and PA +25OHCH caused >20% decrease of HUVEC integrity than fasting serum (P < 0.001). HUVEC disintegration was accompanied by a decrease of occludin mRNA expression as compared with fasting serum (P < 0.05). The fatty meal affected neither VE-cadherin mRNA expression nor its apoptosis (P > 0.05). Mixture of PA +25OHCH caused decrease of VE-cadherin mRNA expression as compared with fasting serum (P < 0.01). PA +25OHCH did not affect HUVEC apoptosis (P > 0.05). Postprandial serum and PA +25OHCH caused increase of IL-33, MCP-1, ICAM-1, IL-32, VEGF, and CX3C-chemokine mRNA expression as compared with fasting serum (P < 0.05). Moreover, level of VEGF in fatty serum was significantly higher (P < 0.001). Postprandial lipemia after a single fatty meal may destabilize the endothelial barrier and initiate inflammatory processes.