Abstract | BACKGROUND: METHODS AND RESULTS: Functional DNAzyme targeting Egr-1 or a size-matched scrambled control were delivered via the intracoronary route immediately on reperfusion after 60 minutes' balloon occlusion of the left anterior descending coronary artery in a pig model of myocardial I/R injury (n=7 per treatment group). Heart function and extent of myocardial infarction were determined following intervention by echocardiography and cardiac magnetic resonance imaging, respectively. Hearts were removed and examined for molecular and histological markers of inflammation and apoptosis. Administration of functional DNAzyme led to an overall decrease in the expression of inflammatory markers including intracellular adhesion molecule-1, tissue factor, and complement 3, with associated decreases in the extent of neutrophil infiltration, oxidative damage, and subsequent apoptosis within the infarct border zone. Functional significance was indicated by an increase in salvaged left ventricular myocardium (P=0.012), ejection fraction (P=0.002), and fractional area change (P=0.039) in the functional DNAzyme-treated group compared with the control. CONCLUSIONS: Egr-1 silencing through intracoronary delivery of a targeting DNAzyme at the time of reperfusion following acute myocardial ischemia decreases myocardial inflammation and apoptosis leading to improved cardiac function.
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Authors | Benjamin S Rayner, Gemma A Figtree, Tharani Sabaretnam, Ping Shang, Jawad Mazhar, James C Weaver, William N Lay, Paul K Witting, Stephen N Hunyor, Stuart M Grieve, Levon M Khachigian, Ravinay Bhindi |
Journal | Journal of the American Heart Association
(J Am Heart Assoc)
Vol. 2
Issue 4
Pg. e000023
(Jul 31 2013)
ISSN: 2047-9980 [Electronic] England |
PMID | 23902638
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Catalytic
- Early Growth Response Protein 1
- Inflammation Mediators
- Oligonucleotides
- RNA, Messenger
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Topics |
- Animals
- Apoptosis
- DNA, Catalytic
(administration & dosage)
- Disease Models, Animal
- Down-Regulation
- Early Growth Response Protein 1
(genetics, metabolism)
- Echocardiography
- Inflammation Mediators
(metabolism)
- Magnetic Resonance Imaging, Cine
- Male
- Myocardial Infarction
(diagnosis, enzymology, genetics, physiopathology, prevention & control)
- Myocardial Reperfusion Injury
(diagnosis, enzymology, physiopathology, prevention & control)
- Myocardium
(enzymology, pathology)
- Neutrophil Infiltration
- Oligonucleotides
(administration & dosage)
- Oxidative Stress
- RNA, Messenger
(metabolism)
- Stroke Volume
- Swine
- Systole
- Time Factors
- Ventricular Dysfunction, Left
(diagnosis, enzymology, genetics, physiopathology, prevention & control)
- Ventricular Function, Left
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