Abstract
Triglyceride-rich lipoprotein (TGRL) lipolysis products provide a pro-inflammatory stimulus that can alter endothelial barrier function. To probe the mechanism of this lipolysis-induced event, we evaluated the pro-inflammatory potential of lipid classes derived from human postprandial TGRL by lipoprotein lipase (LpL). Incubation of TGRL with LpL for 30 min increased the saturated and unsaturated FFA content of the incubation solutions significantly. Furthermore, concentrations of the hydroxylated linoleates 9-hydroxy ocatadecadienoic acid (9-HODE) and 13-HODE were elevated by LpL lipolysis, more than other measured oxylipids. The FFA fractions elicited pro-inflammatory responses inducing TNFalpha and intracellular adhesion molecule expression and reactive oxygen species (ROS) production in human aortic endothelial cells (HAECs). The FFA-mediated increase in ROS was blocked by both the cytochrome P450 2C9 inhibitor sulfaphenazole and NADPH oxidase inhibitors. Compared with linoleate, 13-HODE was found to be a more potent inducer of ROS production in HAECs, an activity that was insensitive to both NADPH oxidase and cytochrome P450 inhibitors. Therefore, although the oxidative metabolism of FFA in endothelial cells can produce inflammatory responses, TGRL lipolysis can also release preformed mediators of oxidative stress (e.g., HODEs) that may influence endothelial cell function in vivo by stimulating intracellular ROS production.
Highlights
Triglyceride-rich lipoprotein (TGRL) lipolysis products provide a pro-inflammatory stimulus that can alter endothelial barrier function
Atherosclerosis is correlated with postprandial hyperlipidemia, which is characterized by elevated TGRL levels in the blood, and there is increasing evidence that postprandial TGRLs are more atherogenic than fasting TGRLs [3, 29,30,31]
We found that postprandial TGRLs, lipolyzed in vitro by purified bovine milk lipoprotein lipase (LpL), injured human aortic endothelial cell (HAEC), induced the expression of inflammatory factors and cytokines [8], stimulated membrane microdomain aggregation, and increased the production of reactive oxygen species (ROS) [18]
Summary
Triglyceride-rich lipoprotein (TGRL) lipolysis products provide a pro-inflammatory stimulus that can alter endothelial barrier function. The oxidative metabolism of FFA in endothelial cells can produce inflammatory responses, TGRL lipolysis can release preformed mediators of oxidative stress (e.g., HODEs) that may influence endothelial cell function in vivo by stimulating intracellular ROS production.—Wang, L., R. Linoleic acid (LA) increases the permeability of human aortic endothelial cells (HAECs) in culture [12,13,14], whereas decreased endothelial nitric oxide synthase activity is produced by palmitate and oleate, but not linoleate [15]. These results suggest that elevations in FAs may contribute to endothe-.
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