Elevated Lipoprotein(a) Levels Lower ABCA1 Cholesterol Efflux Capacity

Hagai Tavori, Alexandra M. Fenton, Deanna L. Plubell, Sara Rosario, Elisabeth Yerkes, Rayna Gasik, Joshua Miles, Paige Bergstrom, Jessica Minnier, Sergio Fazio, Nathalie Pamir

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Context: Elevated serum lipoprotein(a) [Lp(a)] levels are associated with increased cardiovascular disease risk. ABCA1-mediated cholesterol efflux from macrophages may be an antiatherogenic process. Plasminogen (PLG) is a driver of ABCA1-mediated cholesterol efflux, and its action is inhibited by purified human Lp(a). Objective: To determine the effects of Lp(a) in human serum on ABCA1 cholesterol efflux. Methods: Cholesterol efflux capacity (CEC) was measured with two different cell-culture models using serum from 76 patients with either low (<50 mg/dL) or high (>50 mg/dL) Lp(a) levels. Results: Using cAMP-stimulated J774 macrophages or baby hamster kidney fibroblasts overexpressing human ABCA1, we show that CEC was lower in patients with high Lp(a) levels compared with patients with low levels (-30.6%, P = 0.002 vs-24.1%, P < 0.001, respectively). Total-serum CEC negatively correlated with Lp(a) levels (r =-0.433, P = 0.0007 vs r =-0.505, P = 0.0011, respectively). These negative associations persisted after adjusting for serum cholesterol, age, sex, and statin use in a multiple linear regression model (adjusted R2 = 0.413 or 0.405, respectively) and were strengthened when further adjusting for the interaction between Lp(a) and PLG levels (adjusted R2 = 0.465 and 0.409, respectively). Total-serum and isolated Lp(a) from patients with high Lp(a) inhibited PLG-mediated ABCA1 cholesterol efflux. Conclusion: Total-serum CEC is reduced in patients with high Lp(a) levels. This is in part due to the inhibition of PLG-mediated ABCA1 cholesterol efflux by Lp(a). Our findings suggest an atherogenic role for Lp(a) through its ability to inhibit CEC.

Original languageEnglish (US)
Pages (from-to)4793-4803
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume104
Issue number10
DOIs
StatePublished - Oct 1 2019

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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