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Abstract 561: Reduced Serum Efflux Capacity Associates With Elevated Plasma Lp(a) Levels

Authors :
Paige Bergstrom
Deanna L. Plubell
Nathalie Pamir
Hagai Tavori
Jessica Minnier
Sergio Fazio
Alexandra M Fenton
Source :
Arteriosclerosis, Thrombosis, and Vascular Biology. 38
Publication Year :
2018
Publisher :
Ovid Technologies (Wolters Kluwer Health), 2018.

Abstract

Background: Plasminogen, is a potent acceptor of cholesterol by the ABCA1 transporter in peripheral cells, and this function is inhibited by lipoprotein (a) [Lp(a)]. Patients with high Lp(a) have increased cardiovascular disease risk, but the mechanism for this effect is not known. The interplay of plasminogen and Lp(a) in contributing to the total sterol efflux capacity of whole serum (TSEC) could explain the influence of Lp(a) on vascular health. We investigated TSEC in patients with low and high plasma Lp(a) levels. Methods: TSEC (measured in cAMP-stimulated J774 murine macrophages), lipid profile, Lp(a), and plasminogen levels were measured in a cohort of patients (N=58) followed for standard-of-care in our lipid clinic. Weused a linear regression model with sex, age, Lp(a), plasminogen, LDL and HDL cholesterol levels, and use of lipid-lowering drugs to understand the predictors of TSEC. The interaction between plasminogen, ABCA1, and Lp(a) was further characterized by biochemical studies of Lp(a) isoforms, cell based assays, and label free protein-protein interaction assays. Results: TSEC was 30% lower (p=0.002) in patients with plasma Lp(a) levels >50mg/dl compared with those below 50mg/dl. Plasminogen, Lp(a), Lp(a)/plasminogen interaction, and LDL-C were significant predictors of TSEC (adjusted R 2 =0.48, p20mg/dl when compared to samples co-treated with plasma from patients with lower Lp(a) levels. Furthermore, two distinct Lp(a) isoforms isolated from different patients inhibited plasminogen mediated sterol efflux. Finally, label free protein-protein interaction assays showed that plasminogen binds to ABCA1 in a process inhibited by the presence of Lp(a). Conclusion: Our results support an interaction between plasminogen and Lp(a) that contribute to the total sterol efflux capacity of the serum, an atheroprotective process.

Details

ISSN :
15244636 and 10795642
Volume :
38
Database :
OpenAIRE
Journal :
Arteriosclerosis, Thrombosis, and Vascular Biology
Accession number :
edsair.doi...........46e96322518297557a311f965ecea611
Full Text :
https://doi.org/10.1161/atvb.38.suppl_1.561