Abstract 15427: Lipoprotein(a) Proteomic Signatures and Links to Metabolic Pathways

Introduction: High levels of Lp(a) are positively associated with the development of ASCVD. The pathways regulating levels and links to disease are not clear. Lipoprotein(a) has two main proteins: apolipoprotein(a) [apo(a)] and apolipoporoteinB100 (apoB100).The aim of this study was to describe additional proteins on Lp(a) and links to pathways that may drive disease mechanisms.

Methods: We analyzed plasma from 10 healthy volunteers, mean age 47 ±13 years, 50% female (5 Blacks, 3 Hispanics, 2 Whites). Lp(a) was isolated via immunoprecipitation (IP). Two distinct proteome analyses were compared: in-gel versus in-solution digestion of immunoprecipitated Lp(a), in two independent laboratories. Proteins that were identified with at least 3 unique peptides, and present in every IP sample were considered. Biological networks were generated based on protein abundance using the STRING database.

Results: There were 55 proteins identified in every IP sample via in-gel preparation and 92 proteins met the same criteria via in-solution preparation. We found 26 proteins overlapping between the two methods (Table 1A). Apo(a) and apoB100 met the strict criteria we set forth, showing that we successfully immunoprecipitated Lp(a) from plasma. The top gene ontology biological processes and networks associated with the Lp(a) proteome are presented on Table 1B and Figure 1, respectively.

Conclusions: Lp(a) proteome analysis via two platforms provides pathways that can increase our understanding of Lp(a) links to disease mechanisms. Further studies of these protein-protein interactions and their pathways can lead to enhanced understanding of Lp(a) links to ASCVD and other diseases.