Intracoronary delivery of DNAzymes targeting human EGR-1 reduces infarct size following myocardial ischaemia reperfusion

The Journal of Pathology
Ravinay BhindiHarry C Lowe

Abstract

Despite improvements in treatment, myocardial infarction (MI) remains an important cause of morbidity and mortality. Inflammation arising from ischaemic and reperfusion injury is a key mechanism which underpins myocardial damage and impairment of cardiac function. Early growth response-1 (Egr-1) is an early immediate gene and a master regulator that has been implicated in the pathogenesis of ischaemia-reperfusion (IR) injury. This study sought to examine the effect of selective inhibition of Egr-1 using catalytic deoxyribonucleic acid molecules (DNAzymes, DZs) delivered via the clinically relevant coronary route in a large animal model of myocardial IR. It was hypothesized that Egr-1 inhibition with intracoronary DZ would reduce infarction size by modulating its downstream effector molecules. Egr-1 DZs inhibited the adherence of THP-1 monocytes to IL-1β-activated endothelial cells in vitro and retained its catalytic activity up to 225 min after in vivo administration. In a porcine model of myocardial IR (45 min ischaemia/3 h reperfusion), DZ was taken up in the cytoplasm and nuclei of cardiomyocytes and endothelial cells in the myocardium after intracoronary delivery. Egr-1 DZs reduced infarct size and improved cardiac function...Continue Reading

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Citations

Jul 14, 2012·PloS One·Estella Sanchez-GuerreroLevon M Khachigian
Jun 3, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Juan ZhangXiangrui Wang
Feb 22, 2013·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Man ChenLubo Zhang
Mar 17, 2015·Expert Opinion on Biological Therapy·Alesya A FokinaJean-Christophe François
Jun 3, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Levon M Khachigian
Sep 19, 2019·Nucleic Acids Research·Erica A K DePasqualeNathan Salomonis
Feb 15, 2019·Cancer Research·Levon M Khachigian
Feb 4, 2019·Biochemical and Biophysical Research Communications·Fernando S SantiagoLevon M Khachigian
Sep 4, 2021·Journal of the American Heart Association·Fernando S SantiagoLevon M Khachigian

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