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.
Cardiovascular Research Center (CSIC-ICCC), Barcelona, Spain; Sant Pau Biomedical Research Institute Sant Pau, Barcelona, Spain.
Judit
J
Cubedo
Cardiovascular Research Center (CSIC-ICCC), Barcelona, Spain; Sant Pau Biomedical Research Institute Sant Pau, Barcelona, Spain.
Teresa
T
Padró
Cardiovascular Research Center (CSIC-ICCC), Barcelona, Spain; Sant Pau Biomedical Research Institute Sant Pau, Barcelona, Spain; Cardiovascular Research Chair UAB, Barcelona, Spain. Electronic address: lbadimon@csic-iccc.org.
Lina
L
Badimon
D016632:Apolipoprotein A-I / Q000097:blood*; D015153:Blotting, Western; D002241:Carbohydrates / Q000737:chemistry*; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D006031:Glycosylation; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D020543:Proteome; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D016632:Apolipoprotein A-I; D002241:Carbohydrates; D020543:Proteome