Glycosylated apolipoprotein J in cardiac ischaemia: molecular processing and circulating levels in patients with acute ischaemic events. (28th September 2021)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: European heart journal. Volume 43:Number 2(2022)
• Page Start: 153
• Page End: 163
• Publication Date: 2021-09-28
• Subjects: Acute myocardial infarction -- Apolipoprotein J -- Clusterin -- Acute myocardial ischaemia -- Prognosis -- Risk stratification; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehab691
• Languages: English
• ISSNs: 0195-668X

Abstract

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. Graphical Abstract: