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Glycosylated apolipoprotein J in cardiac ischaemia: molecular processing and circulating levels in patients with acute ischaemic events.
Cubedo, Judit; Padró, Teresa; Vilahur, Gemma; Crea, Filippo; Storey, Robert F; Lopez Sendon, Jose Luis; Kaski, Juan Carlos; Sionis, Alessandro; Sans-Rosello, Jordi; Fernández-Peregrina, Estefanía; Gallinat, Alex; Badimon, Lina.
Afiliación
  • Cubedo J; Cardiovascular Program-ICCC-IR, Hospital Santa Creu i Sant Pau, c/Sant Antoni MaClaret 167, 08025 Barcelona, Spain.
  • Padró T; Cardiovascular Program-ICCC-IR, Hospital Santa Creu i Sant Pau, c/Sant Antoni MaClaret 167, 08025 Barcelona, Spain.
  • Vilahur G; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CiberCV), Hospital Santa Creu i Sant Pau, c/Sant Antoni MaClaret 167, 08025 Barcelona, Spain.
  • Crea F; Cardiovascular Program-ICCC-IR, Hospital Santa Creu i Sant Pau, c/Sant Antoni MaClaret 167, 08025 Barcelona, Spain.
  • Storey RF; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CiberCV), Hospital Santa Creu i Sant Pau, c/Sant Antoni MaClaret 167, 08025 Barcelona, Spain.
  • Lopez Sendon JL; Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, Roma 00168, Italy.
  • Kaski JC; Fondazione Policlinico Universitario A. Gemelli IRCCS, Via Giuseppe Moscati, 31, Roma 00168, Italy.
  • Sionis A; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield S10 2RX, UK.
  • Sans-Rosello J; IDIPAZ Research Institute, C. de Pedro Rico, 6, Madrid 28029, Spain.
  • Fernández-Peregrina E; Molecular and Clinical Sciences Research Institute, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
  • Gallinat A; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CiberCV), Hospital Santa Creu i Sant Pau, c/Sant Antoni MaClaret 167, 08025 Barcelona, Spain.
  • Badimon L; Cardiology Department, Hospital Santa Creu i Sant Pau, c/Sant Antoni MaClaret 167, 08025 Barcelona, Spain.
Eur Heart J ; 43(2): 153-163, 2022 01 13.
Article en En | MEDLINE | ID: mdl-34580705
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Clusterina / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Eur Heart J Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Clusterina / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Eur Heart J Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido