Abstract
Clusterin exerts anti-inflammatory, cytoprotective and anti-apoptotic effects. Both an increase and decrease of clusterin in acute myocardial infarction (AMI) has been reported. We aimed to clarify the role of clusterin as a systemic biomarker in AMI. AMI was induced by percutaneous left anterior artery (LAD) occlusion for 90 min followed by reperfusion in 24 pigs. Contrast ventriculography was performed after reperfusion to assess left ventricular ejection fraction (LVEF), left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) and additional cMRI + late enhancement to measure infarct size and LV functions at day 3 and week 6 post-MI. Blood samples were collected at prespecified timepoints. Plasma clusterin and other biomarkers (cTnT, NT-proBNP, neprilysin, NGAL, ET-1, osteopontin, miR21, miR29) were measured by ELISA and qPCR. Gene expression profiles of infarcted and remote region 3 h (n = 5) and 3 days (n = 5) after AMI onset were analysed by RNA-sequencing. AMI led to an increase in LVEDV and LVESV during 6-week, with concomitant elevation of NT-proBNP 3-weeks after AMI. Plasma clusterin levels were increased immediately after AMI and returned to normal levels until 3-weeks. Plasma NGAL, ET-1 and miR29 was significantly elevated at 3 weeks follow-up, miR21 increased after reperfusion and at 3 weeks post-AMI, while circulating neprilysin levels did not change. Elevated plasma clusterin levels 120 min after AMI onset suggest that clusterin might be an additional early biomarker of myocardial ischemia.
Highlights
Diagnosis and therapy of acute myocardial infarction (AMI) are essential to reduce infarct size and improve prognosis [1,2,3]
We demonstrate increased plasma clusterin levels after ischemic myocardial injury (120 min after AMI onset) that returned to normal levels already after 3 days, suggesting that it can be a similar and early and high-sensitive biomarker of acute myocardial ischemia as high-sensitivity cardiac troponin (hs-cTn), which increases 2–3 h after ischemia onset and remains elevated
We demonstrate increased plasma clusterin levels after ischemic myocardial injury (120 min after AMI onset) that returned to normal levels already after 3 days, suggesting that it can be a similar and early and high-sensitive biomarker of acute myocardial ischemia as hs-cTn, which increases 2–3 h after ischemia onset and remains elevated several days after AMI
Summary
Diagnosis and therapy of acute myocardial infarction (AMI) are essential to reduce infarct size and improve prognosis [1,2,3]. Current gold standard of early diagnosis of AMI is high-sensitivity cardiac troponin (hs-cTn), [4] even though this marker has several limitations [5]. It has restricted specificity with an increase in non-ischemic injuries, such as pulmonary oedema, or embolisation, anticancer treatment or chronic kidney disease [6]. Clusterin levels are up-regulated under conditions of cell stress and tissue injury and in patients suffering from myocardial infarction, dialyses-related amyloidosis, atherosclerosis, cancer, diabetes and neurodegenerative diseases [9]. In the early and later stage of myocardial ischemia, plasma clusterin levels are found to be both increased and decreased [8,13]. Clusterin has been applied therapeutically in animal studies [17]
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