Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm

Abstract

High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas α-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA.

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

“…Downloaded from http://ahajournals.org by on April 30, 2019 in the pathogenesis of AAA. 25,31 Interestingly, in a previous study of 10 patients, peroxiredoxin-1 was found to be increased in the luminal compared with the abluminal part of the ILT. 24 The abundant erythrocytes in the luminal part of the ILT deliver an endless supply of cells that generate reactive oxidative species.…”

What is the blood concentration of extracellular vesicles? Implications for the use of extracellular vesicles as blood-borne biomarkers of cancer

“…For example, advances in proteomics have extended the list of HDL-associated proteins, beyond the apolipoproteins associated to HDL, to over 85 suggesting that the composition of HDL is more complex than previously anticipated [69]. Studies have also shown that the levels of specific HDL-associated proteins are altered in disease states [86,87] and in polluted environments [88], and could therefore potentially also be used as disease biomarkers [89]. LDL and VLDL are also associated with a growing number of associated proteins that are known to have important functions in dyslipidemia, atherosclerosis, and coagulation disorders [90].…”

The phospholipase A2 activity of peroxiredoxin 6 [S]

“…Prdx6 content in blood serum was increased in ~50% of patients with Crohn's disease (161). Tissue and plasma levels of Prdx6 have been proposed as a biomarker for human abdominal aortic aneurysm (162). Lung…”