In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. suppl_2 ( 2014-11-25)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.130.suppl_2.16069
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2014
detail.hit.zdb_id:
1466401-X
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