Lp(a) lipidomics and proteomics-emerging from the shadows

Lars Berglund

1,*

Sally McCormick

Katie Peppercorn

Byambaa Enkhmaa

*Correspondence to: Lars Berglund, Department of Internal Medicine, University of California Davis, Davis, CA 95616, USA. E-mail: lberglund@ucdavis.edu

Adv Lipoprotein(a) Res. 2026;1:202611. 10.70401/alr.2026.0013

Received: July 10, 2026Accepted: November 04, 2026Published: November 05, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Lipoprotein(a) [Lp(a)] is a major cardiovascular risk factor. In contrast to the genetic regulation of apo(a) and its effect on Lp(a) levels, the lipidomic and proteomic properties of Lp(a) have attracted far less attention. Lp(a) is the main carrier of oxidized phospholipids (OxPL), the major portion being phosphatidylcholine residues, in particular PONPC or ALDO-PC. While Lp(a) levels increase with a reduction in saturated fat intake, findings regarding Lp(a)-OxPL concentrations have varied, some studies finding an increase and others a decrease. Lp(a)-TG levels vary substantially depending on the individual triglyceridemia status. More than 440 lipid species have been identified in Lp(a) lipidomic analyses, and 20% of these change during dietary modification, suggesting a high degree of variability in the Lp(a) lipid composition and that it is impacted by metabolic conditions. The proteomic properties of Lp(a) have been reported in several studies and while much variation in protein content is evident, a consensus Lp(a) proteome of 46 proteins can be derived. A functional network analysis of these proteins showed two major clusters, one of “plasma lipoprotein particle” proteins, and another of “complement and coagulation cascade” proteins with a third minor cluster containing “complement activation pathway” proteins. A significant number of proteins across all three clusters were classified as proinflammatory. Comparisons between the LDL and Lp(a) proteomes show Lp(a) to have a more diverse protein makeup. The Lp(a) lipidomic and proteomic properties found to date offer unique avenues to explore properties contributing to its risk factor role.

Keywords

Lipoprotein(a), lipoprotein metabolism, nutrition, cardiovascular risk, proteomics, inflammation

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Berglund L, McCormick S, Peppercorn K, Enkhmaa B. Lp(a) lipidomics and proteomics-emerging from the shadows. Adv Lipoprotein(a) Res. 2026;1:202611. https://doi.org/10.70401/alr.2026.0013