Glycoproteome of human apolipoprotein A-I: N- and O-glycosylated forms are increased in patients with acute myocardial infarction

High-density lipoprotein (HDL) functionality, which is closely associated with its composition and transport capabilities, determines its role in atheroprotection. During acute phase processes, HDL seems to lose its anti-inflammatory and cytoprotective properties. In this study, we hypothesized that after an acute myocardial infarction apolipoprotein (Apo) A-I, the main protein component of HDL, might undergo changes in its molecular processing. Therefore, we have characterized the Apo A-I proteome during the evolution of new-onset acute myocardial infarction (AMI). To this end, serum Apo A-I was characterized by 2-dimensional electrophoresis/mass-spectrometry in controls and AMI patients at admission (within the first 6 hours after pain onset) and 8 hours, 16 hours, 24 hours, and 3 days afterward. The Apo A-I glycoproteome was analyzed by lectin-based glycoprotein isolation methods and deglycosylation assays, and Apo A-I serum levels were evaluated by enzyme-linked immunosorbent assay (ELISA). The Apo A-I proteomic signature (5 spots: 28 kDa/pI:5-5.75) was significantly altered in AMI patients 3 days after the event with respect to controls. Increased levels of N- and O-glycosylated Apo A-I forms were found post-AMI. Apo A-I serum levels measured by ELISA were significantly changed and related to left ventricular ejection fraction, troponin-T, and C-reactive protein. The Apo A-I molecule measured by ELISA corresponded to the main glycosylated spots and was specifically O-GlcNAcylated in AMI patients. Therefore, our results demonstrate that Apo A-I is both N- and O-glycosylated and that there is an increase in Apo A-I glycosylation after AMI. Furthermore, the specific increase in the O-GlcNAcylated forms could have a relevant prognostic value and a protective role in the evolution of AMI. High-density lipoprotein (HDL) functionality, which is closely associated with its composition and transport capabilities, determines its role in atheroprotection. During acute phase processes, HDL seems to lose its anti-inflammatory and cytoprotective properties. In this study, we hypothesized that after an acute myocardial infarction apolipoprotein (Apo) A-I, the main protein component of HDL, might undergo changes in its molecular processing. Therefore, we have characterized the Apo A-I proteome during the evolution of new-onset acute myocardial infarction (AMI). To this end, serum Apo A-I was characterized by 2-dimensional electrophoresis/mass-spectrometry in controls and AMI patients at admission (within the first 6 hours after pain onset) and 8 hours, 16 hours, 24 hours, and 3 days afterward. The Apo A-I glycoproteome was analyzed by lectin-based glycoprotein isolation methods and deglycosylation assays, and Apo A-I serum levels were evaluated by enzyme-linked immunosorbent assay (ELISA). The Apo A-I proteomic signature (5 spots: 28 kDa/pI:5-5.75) was significantly altered in AMI patients 3 days after the event with respect to controls. Increased levels of N- and O-glycosylated Apo A-I forms were found post-AMI. Apo A-I serum levels measured by ELISA were significantly changed and related to left ventricular ejection fraction, troponin-T, and C-reactive protein. The Apo A-I molecule measured by ELISA corresponded to the main glycosylated spots and was specifically O-GlcNAcylated in AMI patients. Therefore, our results demonstrate that Apo A-I is both N- and O-glycosylated and that there is an increase in Apo A-I glycosylation after AMI. Furthermore, the specific increase in the O-GlcNAcylated forms could have a relevant prognostic value and a protective role in the evolution of AMI. N-Glycosylation of apolipoprotein A1 in cardiovascular diseasesTranslational ResearchVol. 165Issue 2PreviewA very interesting paper by Cubedo et al1 has been recently published "Glycoproteome of human Apo A-I: N- and O-glycosylated forms are increased in acute myocardial infarction patients," which significantly contributes to our field in the clinical application of proteomics in cardiovascular diseases. The authors demonstrated (among other results) that both the N- and O-glycosylation of apolipoprotein A1 (apoA1) changed in patient plasma during the first 3 days after an acute myocardial infarction (AMI) event. Full-Text PDF