Glycoproteomic Profiling Provides Candidate Myocardial Infarction Predictors of Later Progression to Heart Failure

Abstract

We hypothesized that identifying plasma glycoproteins that predict the development of heart failure following myocardial infarction (MI) could help to stratify subjects at risk. Plasma collected at visit 2 (2005–2008) from an MI subset of Jackson Heart Study participants underwent glycoproteomics and was grouped by the outcome: (1) heart failure hospitalization after visit 2 (n = 15) and (2) without hospitalization by 2012 (n = 45). Proteins were mapped for biological processes and functional pathways using Ingenuity Pathway Analysis and linked to clinical characteristics. A total of 198 glycopeptides corresponding to 88 proteins were identified (data available via ProteomeXchange with identifier PXD009870). Of these, 14 glycopeptides were significantly different between MI and MI + HF groups and corresponded to apolipoprotein (Apo) F, transthyretin, Apo C-IV, prostaglandin-D2 synthase, complement C9, and CD59 (p < 0.05 for all). All proteins were elevated in the MI + HF group, except CD59, which was lower. Four canonical pathways were upregulated in the MI + HF group (p < 0.05 for all): acute phase response, liver X receptor/retinoid X receptor, and macrophage reactive oxygen species generation. The coagulation pathway was significantly downregulated in the MI + HF group (p < 0.05). Even after adjustment for age and sex, Apo F was associated with the increased risk for heart failure (OR = 21.84; 95% CI 3.20–149.14). In conclusion, glycoproteomic profiling provided candidate early MI predictors of later progression to heart failure.

Apolipoprotein Proteomic Profiling for the Prediction of Cardiovascular Death in Patients with Heart Failure

“…[9] More recently, Deleon-Pennell et al found, using a glycoproteomic profiling, that Apo-F is independently associated with the risk of later progression to HF after myocardial infarction in humans. [26] Finally, we previously published that Apo-J is involved in cardiac cell hypertrophy and is a potential biomarker of left ventricular remodeling following myocardial infarction. [27] More recently, we showed that this increased levels of Apo-J is due to a defect in protein degradation systems activity.…”

A Mass Spectrometry-Based Proteome Study of Twin Pairs Discordant for Incident Acute Myocardial Infarction within Three Years after Blood Sampling Suggests Novel Biomarkers

“…Of the seven proteins passing correction for multiple testing, three have previously been put forward as cardiovascular makers: apolipoprotein C-IV (APOC4) is a lipid-binding protein belonging to the apolipoprotein gene family, and the gene is located in the so-called APOE - APOC1 - APOC4 - APOC2 gene cluster, which has been intensively studied in relation to cardiovascular traits and risk factors, e.g., [ 23 ]. With respect to proteome studies, APOC4 has been reported to be associated with coronary atherosclerosis [ 24 ], heart failure after AMI [ 25 ], and recovery from stroke [ 26 ]. Additionally, lipopolysaccharide-binding protein (LBP) has been reported as a protein marker of AMI [ 13 ] and to be associated with coronary atherosclerotic plaque disruption [ 27 ], as well as a risk of AMI after human immunodeficiency virus [ 28 ] or COVID-19 infection [ 29 ].…”

Multi‐omic analyses and network biology in cardiovascular disease

“…Glycoproteomic analysis of human atrial extracellular matrix proteins, using lectin‐based glycoprotein enrichment, identified 65 N ‐ and O ‐linked glycosylation sites in 35 proteins, with several showing differential expression between the left and right atria [116]. PTMs also show putative potential as biomarkers of heart failure, with 14 of 198 glycopeptides identified in human plasma showing differential expression in post‐MI patients who required subsequent rehospitalization versus those who did not [117], suggesting candidate glycoproteins as predictors of future heart failure progression.…”