Apo A1 shows post-translational guanidinylation in CVD patients

Abstract-Text (inkl. Referenzen und Bildunterschriften)

Background and Aims: High-density lipoproteins (HDL) are well-known cardioprotective mediators. Dysfunctional HDL strongly contributes to increased cardiovascular mortality in chronic kidney disease (CKD) patients. Post-translational modifications (PTMs) of HDL proteins can lead to functional impairments of HDL. However, there is a lack of conclusive molecular data on the occurrence of PTMs in HDL from CKD and CVD patients compared to HDL isolated from healthy controls. Therefore, this study aimed to analyze PTMs major HDL protein apolipoprotein A-I (apo A-I) in these cohorts.

Methods: The prevalence of PTMs of apo A-1 from CKD with kardiovaskulare disease patients at KDIGO stages 1-5, as well as from healthy controls, were analyzed by mass spectrometry. The plasma proteins were purified, desalted by chromatography, and analyzed by MALDI-TOF-MS following MS/MS analyses. The resulting mass-spectrometric data were compared with the MASCOT database (Matrix Science, UK). In addition, authentic human apolipoprotein A-1 (Sigma Aldrich, Germany) was invitro modified by incubation with guanidine and analyzed by the identical mass-spectrometric approach.

Results: This mass-spectrometric approach identified post-translational guanidinylations of apolipoprotein A-1. The number of post-translational guanidinylations of apolipoprotein A-1 in plasma from CVD patients increased in advanced CKD stages. The identification of post-translational guanidinylations of apolipoprotein A-1 was validated by incubating apolipoprotein A-1 with guanindine and mass-spectrometric analyses.

Conclusion: In an ongoing clinical study, the pathophysiological consequences of guanidinylated apo A-I are analyzed.