Abstract 16069: Low-Density Lipoprotein of Systemic Lupus Erythematosus Patients Contains Lysophosphatidylcholine-Rich Lipid That Induces Overexpression of CX3CL1 in Endothelial Cells
Background: Patients with systemic lupus erythematosus (SLE) are twice more likely to develop cardiovascular disease than the general population, even though their plasma LDL cholesterol (LDL-C) levels are usually not elevated. To delineate the mechanisms, we examined the chemical properties of their LDL.
Methods and Results: LDL isolated from SLE patients (LDL-C, 105±33 mg/dL; n=24) exhibited greater mobility in agarose gel electrophoresis than LDL of healthy control subjects (LDL-C, 121±25 mg/dL; n=24), secondary to an increased distribution of L5 (2.30±1.3% vs. 0.7±0.3%; P<0.0001), the most electronegative subfraction of LDL identified by anion-exchange chromatography, in total LDL. CX3CL1 is a membrane-bound chemokine expressed in injured endothelial cells (ECs). CD16+ monocytes are CX3CR1-expressing cells that recognize CX3CL1. Compared with control, SLE patients had a twofold (P<0.001) increase in CX3CL1 and a threefold (P<0.0001) increase in CD16+ monocytes in the plasma. Moreover, there was a positive correlation between the CX3CL1 and L5 levels (R=0.45; P<0.018). MALDI/TOF mass spectrometry of the lipid extracted from SLE-LDL revealed a shift from phosphatidylcholines (PCs) to lyso-PCs (LPCs), including m/z 496.33, 524.36, 537.01, 550.94, when compared with the lipid of control LDL (Figure). The shift was especially prominent in L5. Exposing human aortic ECs to L5 but not normal LDL resulted in a fivefold (P<0.0001) increase in CX3CL1 expression with concomitant apoptosis. These effects of L5 were significantly attenuated by blocking the platelet-activating receptor, confirming the role of phospholipids in L5’s bioactivity.
Conclusions: The increased distribution of LPC-rich electronegative LDL, which induces CX3CL1-CX3CR1 interactions between vascular cells, may contribute to the increased cardiovascular disease prevalence in SLE in the absence of LDL-C elevation.
Author Disclosures: H. Chan: None. L. Ke: None. H. Chan: None. H. Su: None. A. Lee: None. J. Lu: None. W. Tsai: None. T. Ou: None. C. Wu: None. C. Chu: None. J. Shiea: None. J. Yen: None. C. Chen: None.
- © 2014 by American Heart Association, Inc.