Quantitative proteomics of lipoproteins: insights into individual differences of lipoprotein associated proteins in the context of cardiovascular disease. — ASN Events
  1. Schedule
  2. Symposium Eight: Disease Proteomics
  3. Quantitative proteomics of lipoproteins: insights into individual differences of lipoprotein associated proteins in the context of cardiovascular disease.

Quantitative proteomics of lipoproteins: insights into individual differences of lipoprotein associated proteins in the context of cardiovascular disease. (#032)

Anne von Zychlinski 1 , Michael Williams 2 , Sally McCormick 1 , Torsten Kleffmann 3
  1. Department of Biochemistry, University of Otago, Dunedin, New Zealand
  2. Department of Medicine, University of Otago, Dunedin, New Zealand
  3. Centre for Protein Research, Department of Biochemistry, University of Otago, Dunedin, New Zealand

A disordered balance between plasma lipoproteins is a major risk factor for developing cardiovascular disease (CVD). High plasma levels of Lipoprotein(a) (Lp(a)) is another, independent risk factor for developing premature CVD. Various underlying disease mechanisms are not fully understood and details of Lp(a) physiology are still unclear.

We utilised different quantitative proteomics approaches to gain further insights into the biochemistry and pathophysiology of different lipoproteins with a main focus on Lp(a). Using absolute quantification (AQUA) of proteins by mass spectrometry we elucidated the stoichiometry of proteins per particle for the different lipoprotein classes. We then  quantified the protein cargo of Lp(a) isolated from a cohort of 40 subjects using SWATH-MS in conjunction with AQUA.

The AQUA approach provided accurate numbers of lipoprotein-associated proteins per particle and showed significant individual differences in the apolipoprotein profiles of various particle classes such as strong variations in the numbers of apoC1, apoC2 and apoC3, which may indicate alterations in triglyceride metabolism. Proteins involved in immune response and complement activation which have been discussed in the context of lipoprotein-related CVD risk were only detected in very low numbers. Quantification of Lp(a)-associated proteins using AQUA and SWATH-MS identified a group of subjects with high levels of Lp(a)-associated histidine-rich glycoprotein (HRG). Those subjects also showed significantly higher levels of known HRG-interactors that are involved in coagulation and immune response. We hypothesise that Lp(a)-HRG interaction competes with HRG-plasminogen promoted regulation of fibrinolysis at sites of atherosclerotic plaques. However, in the low number of investigated subjects we could not detect any correlation of HRG-rich Lp(a) with disease associated factors such as high Lp(a) levels, high triglyceride levels or CVD events. More detailed information about the biochemistry of Lp(a)-HRG interactions is required and first insights into the influence of the apolipoprotein(a) isoforms on the HRG-interaction will be presented.