Proteomics of Lipoprotein(a) identifies a protein complement associated with response to wounding

Abstract

Lipoprotein(a) [Lp(a)] is a major independent risk factor for cardiovascular disease. Twenty percent of the general population exhibit levels above the risk threshold highlighting the importance for clinical and basic research. Comprehensive proteomics of human Lp(a) will provide significant insights into Lp(a) physiology and pathogenicity. Using liquid chromatography-coupled mass spectrometry, we established a high confidence Lp(a) proteome of 35 proteins from highly purified particles. Protein interaction network analysis and functional clustering revealed proteins assigned to the two major biological processes of lipid metabolism and response to wounding. The latter includes the processes of coagulation, complement activation and inflammatory response. Furthermore, absolute protein quantification of apoB-100, apo(a), apoA1, complement C3 and PON1 gave insights into the compositional stoichiometry of associated proteins per particle. Our proteomics study has identified Lp(a)-associated proteins that support a suggested role of Lp(a) in response to wounding which points to mechanisms of Lp(a) pathogenicity at sites of vascular injury and atherosclerotic lesions. This study has identified a high confidence Lp(a) proteome and provides an important basis for further comparative and quantitative analyses of Lp(a) isolated from greater numbers of plasma samples to investigate the significance of associated proteins and their dynamics for Lp(a) pathogenicity.