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

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 ar...

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Main Authors: Denise Traxler, Andreas Spannbauer, Patrick Einzinger, Julia Mester-Tonczar, Dominika Lukovic, Johannes Winkler, Katrin Zlabinger, Alfred Gugerell, Ljubica Mandic, Mariann Gyöngyösi, Noemi Pavo
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/21/13/4591
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author Denise Traxler
Andreas Spannbauer
Patrick Einzinger
Julia Mester-Tonczar
Dominika Lukovic
Johannes Winkler
Katrin Zlabinger
Alfred Gugerell
Ljubica Mandic
Mariann Gyöngyösi
Noemi Pavo
author_facet Denise Traxler
Andreas Spannbauer
Patrick Einzinger
Julia Mester-Tonczar
Dominika Lukovic
Johannes Winkler
Katrin Zlabinger
Alfred Gugerell
Ljubica Mandic
Mariann Gyöngyösi
Noemi Pavo
author_sort Denise Traxler
collection DOAJ
description 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 (<i>n</i> = 5) and 3 days (<i>n</i> = 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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spelling doaj.art-4981763292194b08ae9ab09bedb71cde2023-11-20T05:11:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012113459110.3390/ijms21134591Early Elevation of Systemic Plasma Clusterin after Reperfused Acute Myocardial Infarction in a Preclinical Porcine Model of Ischemic Heart DiseaseDenise Traxler0Andreas Spannbauer1Patrick Einzinger2Julia Mester-Tonczar3Dominika Lukovic4Johannes Winkler5Katrin Zlabinger6Alfred Gugerell7Ljubica Mandic8Mariann Gyöngyösi9Noemi Pavo10Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Information Systems Engineering, Research Unit of Information and Software Engineering, Vienna University of Technology, 1040 Vienna, AustriaDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaDivision of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, AustriaClusterin 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 (<i>n</i> = 5) and 3 days (<i>n</i> = 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.https://www.mdpi.com/1422-0067/21/13/4591acute myocardial infarctionclusterinNGSmiRNAs
spellingShingle Denise Traxler
Andreas Spannbauer
Patrick Einzinger
Julia Mester-Tonczar
Dominika Lukovic
Johannes Winkler
Katrin Zlabinger
Alfred Gugerell
Ljubica Mandic
Mariann Gyöngyösi
Noemi Pavo
Early Elevation of Systemic Plasma Clusterin after Reperfused Acute Myocardial Infarction in a Preclinical Porcine Model of Ischemic Heart Disease
International Journal of Molecular Sciences
acute myocardial infarction
clusterin
NGS
miRNAs
title Early Elevation of Systemic Plasma Clusterin after Reperfused Acute Myocardial Infarction in a Preclinical Porcine Model of Ischemic Heart Disease
title_full Early Elevation of Systemic Plasma Clusterin after Reperfused Acute Myocardial Infarction in a Preclinical Porcine Model of Ischemic Heart Disease
title_fullStr Early Elevation of Systemic Plasma Clusterin after Reperfused Acute Myocardial Infarction in a Preclinical Porcine Model of Ischemic Heart Disease
title_full_unstemmed Early Elevation of Systemic Plasma Clusterin after Reperfused Acute Myocardial Infarction in a Preclinical Porcine Model of Ischemic Heart Disease
title_short Early Elevation of Systemic Plasma Clusterin after Reperfused Acute Myocardial Infarction in a Preclinical Porcine Model of Ischemic Heart Disease
title_sort early elevation of systemic plasma clusterin after reperfused acute myocardial infarction in a preclinical porcine model of ischemic heart disease
topic acute myocardial infarction
clusterin
NGS
miRNAs
url https://www.mdpi.com/1422-0067/21/13/4591
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