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Cubedo J, Padró T, Vilahur G, et al. Glycosylated apolipoprotein J in cardiac ischaemia: molecular processing and circulating levels in patients with acute ischaemic events. Eur Heart J. 2022;43(2):153-163doi: 10.1093/eurheartj/ehab691.
Cubedo, J., Padró, T., Vilahur, G., Crea, F., Storey, R. F., Lopez Sendon, J. L., Kaski, J. C., Sionis, A., Sans-Rosello, J., Fernández-Peregrina, E., Gallinat, A., & Badimon, L. (2022). Glycosylated apolipoprotein J in cardiac ischaemia: molecular processing and circulating levels in patients with acute ischaemic events. European heart journal, 43(2), 153-163. https://doi.org/10.1093/eurheartj/ehab691
Cubedo, Judit, et al. "Glycosylated apolipoprotein J in cardiac ischaemia: molecular processing and circulating levels in patients with acute ischaemic events." European heart journal vol. 43,2 (2022): 153-163. doi: https://doi.org/10.1093/eurheartj/ehab691
Cubedo J, Padró T, Vilahur G, Crea F, Storey RF, Lopez Sendon JL, Kaski JC, Sionis A, Sans-Rosello J, Fernández-Peregrina E, Gallinat A, Badimon L. Glycosylated apolipoprotein J in cardiac ischaemia: molecular processing and circulating levels in patients with acute ischaemic events. Eur Heart J. 2022 Jan 13;43(2):153-163. doi: 10.1093/eurheartj/ehab691. PMID: 34580705.
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Eur Heart J. 2022 Jan 13;43(2):153-163. doi: 10.1093/eurheartj/ehab691.

Glycosylated apolipoprotein J in cardiac ischaemia: molecular processing and circulating levels in patients with acute ischaemic events.

European heart journal

Judit Cubedo, Teresa Padró, Gemma Vilahur, Filippo Crea, Robert F Storey, Jose Luis Lopez Sendon, Juan Carlos Kaski, Alessandro Sionis, Jordi Sans-Rosello, Estefanía Fernández-Peregrina, Alex Gallinat, Lina Badimon

Affiliations

  1. Cardiovascular Program-ICCC-IR, Hospital Santa Creu i Sant Pau, c/Sant Antoni MaClaret 167, 08025 Barcelona, Spain.
  2. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CiberCV), Hospital Santa Creu i Sant Pau, c/Sant Antoni MaClaret 167, 08025 Barcelona, Spain.
  3. Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, Roma 00168, Italy.
  4. Fondazione Policlinico Universitario A. Gemelli IRCCS, Via Giuseppe Moscati, 31, Roma 00168, Italy.
  5. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield S10 2RX, UK.
  6. IDIPAZ Research Institute, C. de Pedro Rico, 6, Madrid 28029, Spain.
  7. Molecular and Clinical Sciences Research Institute, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
  8. Cardiology Department, Hospital Santa Creu i Sant Pau, c/Sant Antoni MaClaret 167, 08025 Barcelona, Spain.
  9. Autonomous University of Barcelona, Bellaterra 08193, Spain.

PMID: 34580705 DOI: 10.1093/eurheartj/ehab691

Abstract

AIM: Using proteomics, we previously found that serum levels of glycosylated (Glyc) forms of apolipoprotein J (ApoJ), a cytoprotective and anti-oxidant protein, decrease in the early phase of acute myocardial infarction (AMI). We aimed to investigate: (i) ApoJ-Glyc intracellular distribution and secretion during ischaemia; (ii) the early changes in circulating ApoJ-Glyc during AMI; and (iii) associations between ApoJ-Glyc and residual ischaemic risk post-AMI.

METHODS AND RESULTS: Glycosylated apolipoprotein J was investigated in: (i) cells from different organ/tissue origin; (ii) a pig model of AMI; (iii) de novo AMI patients (n = 38) at admission within the first 6 h of chest pain onset and without troponin T elevation at presentation (early AMI); (iv) ST-elevation myocardial infarction patients (n = 212) who were followed up for 6 months; and (v) a control group without any overt cardiovascular disease (n = 144). Inducing simulated ischaemia in isolated cardiac cells resulted in an increased intracellular accumulation of non-glycosylated ApoJ forms. A significant decrease in ApoJ-Glyc circulating levels was seen 15 min after ischaemia onset in pigs. Glycosylated apolipoprotein J levels showed a 45% decrease in early AMI patients compared with non-ischaemic patients (P < 0.0001), discriminating the presence of the ischaemic event (area under the curve: 0.934; P < 0.0001). ST-elevation myocardial infarction patients with lower ApoJ-Glyc levels at admission showed a higher rate of recurrent ischaemic events and mortality after 6-month follow-up (P = 0.008).

CONCLUSIONS: These results indicate that ischaemia induces an intracellular accumulation of non-glycosylated ApoJ and a reduction in ApoJ-Glyc secretion. Glycosylated apolipoprotein J circulating levels are reduced very early after ischaemia onset. Its continuous decrease indicates a worsening in the evolution of the cardiac event, likely identifying patients with sustained ischaemia after AMI.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected].

Keywords: Acute myocardial infarction; Acute myocardial ischaemia; Apolipoprotein J; Clusterin; Prognosis; Risk stratification

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