Abstract 9179: Free Oxidized Fatty Acids Contribute to Pro-Inflammatory HDL
Background: Based on previous studies we thought it likely that the content of oxidized phospholipids would be elevated in pro-inflammatory HDL. While total plasma levels of oxidized phospholipids were increased in mouse models of atherosclerosis and in humans with coronary heart disease (CHD), the content of these oxidized phospholipids in HDL was NOT increased. This led us to look for other lipid components of HDL that might contribute to pro-inflammatory HDL.
Methods &Results: HDL was isolated from sucrose-cryopreserved plasma by ultracentrifugation in the presence of anti-oxidants. The content of free 5-HETE, 9-HETE, 12-HETE, 15-HETE, 9-HODE, and 13-HODE were determined by LC-MS/MS and found to be significantly (p<0.0001; p = 0.0008; p = 0.0289; p = 0.0028; p = 0.0052; and p = 0.0029, respectively) elevated in HDL of 10 patients with CHD (all of whom had pro-inflammatory HDL as determined by cell-based assay) compared to 10 healthy controls (all of whom had anti-inflammatory HDL as determined by cell-based assay). To determine if free oxidized fatty acids contributed to the formation of pro-inflammatory HDL these oxidized fatty acids were added to anti-inflammatory HDL in amounts similar to that found in the CHD patients. The addition of 5-HETE, 9-HETE, and 15-HETE significantly (p = 0.0199; p = 0.0249; p = 0.0382, respectively) reduced the ability of the anti-inflammatory HDL to inhibit cytokine production in cultures of human aortic endothelial cells exposed to oxidized phospholipids. In contrast, addition of saturated non-oxidized free fatty acids such as decanoic or stearic acid did not alter the anti-inflammatory properties of HDL.
Conclusions: These results suggest that i) HDL from CHD patients contains elevated levels of free oxidized fatty acids; ii) Free oxidized fatty acids can convert anti-inflammatory HDL to pro-inflammatory HDL.
- © 2011 by American Heart Association, Inc.