Effects of Triglyceride‐Rich Lipoproteins on the Inflammatory Potential of Endothelial Cells

Abstract

Atherosclerosis, a chronic inflammatory arterial disease featured by focal accumulation of fat‐laden deposits, is exacerbated by prolonged circulation of elevated levels of triglyceride‐rich lipoproteins (TGRL). This study aims to examine the effects of TGRL on the inflammatory potential of endothelial cells and the mechanisms for enhanced recruitment of mononuclear cells using vascular mimetics. We have developed an ex vivo atherogenesis model, in which human aortic endothelial cells (HAEC) in culture are perfused with postprandial TGRL freshly isolated from high‐fat diet fed individuals under varied shear rates. The expressions of cell adhesion molecules (CAM) are examined by flow cytometry, while the binding and internalization of TGRL are visualized by immunofluorescence. The results show an enhanced CAM upregulation upon TNF‐stimulation in TGRL perfused HAECs. Moreover, a member of low density lipoprotein receptors, LR11 is found involved in TGRL binding and upregulated in TNF‐α stimulated HAECs. We conclude that excessive exposure of endothelium to TGRL primes them for enhanced inflammatory response to cytokines or pro‐athero shear flow profiles. This elevated inflammatory state further enhances the recruitment of TGRL, thus revealing a positive feedback loop for metabolically driven development of atherosclerosis.This study is supported by NIH RO1 HL 082689 to S.I.S.