Early Elevation of Systemic Plasma Clusterin After Reperfused Acute Myocardial Infarction in a Preclinical Porcine Model of Ischemic Heart Disease

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Jul 2

PMID 32605184

Citations 3

Authors

Denise Traxler

Andreas Spannbauer

Patrick Einzinger

Julia Mester-Tonczar

Dominika Lukovic

Johannes Winkler

Katrin Zlabinger

Alfred Gugerell

Ljubica Mandic

Mariann Gyongyosi

Noemi Pavo

Affiliations

Soon will be listed here.

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 ( = 5) and 3 days ( = 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.

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