MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs

Prompt coronary catheterization and revascularization have markedly improved the outcomes of myocardial infarction, but have also resulted in a growing number of surviving patients with permanent structural damage of the heart, which frequently leads to heart failure. There is an unmet clinical need...

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) Vol. 569; no. 7756; pp. 418 - 422
Main Authors: Gabisonia, Khatia, Prosdocimo, Giulia, Aquaro, Giovanni Donato, Carlucci, Lucia, Zentilin, Lorena, Secco, Ilaria, Ali, Hashim, Braga, Luca, Gorgodze, Nikoloz, Bernini, Fabio, Burchielli, Silvia, Collesi, Chiara, Zandonà, Lorenzo, Sinagra, Gianfranco, Piacenti, Marcello, Zacchigna, Serena, Bussani, Rossana, Recchia, Fabio A., Giacca, Mauro
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.05.2019
Nature Publishing Group
Subjects:
13/1
13/2
13/44
13/89
14/19
38
38/71
38/89
42/44
631/337/384/331
631/61
64
Animals
Cardiac function
Cardiomyocytes
Care and treatment
Catheterization
Cell cycle
Cell Proliferation - genetics
Congestive heart failure
Control
Death, Sudden, Cardiac - etiology
Gene therapy
Genetic aspects
Health aspects
Heart
Heart - physiology
Heart - physiopathology
Heart attack
Heart attacks
Heart failure
Hogs
Humanities and Social Sciences
Infiltration
Kinases
Letter
Male
Methods
MicroRNA
MicroRNAs
MicroRNAs - administration & dosage
MicroRNAs - adverse effects
MicroRNAs - genetics
MicroRNAs - therapeutic use
miRNA
Mitral valve repair
Morphology
multidisciplinary
Muscle contraction
Muscles
Musculoskeletal system
Myocardial infarction
Myocardial Infarction - genetics
Myocardial Infarction - pathology
Myocardial Infarction - physiopathology
Myocardial Infarction - therapy
Myocytes, Cardiac - cytology
Myocytes, Cardiac - metabolism
NMR
Nuclear magnetic resonance
Phenotypes
Regeneration - genetics
Repair
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Structural damage
Suidae
Sus scrofa - genetics
Swine
Therapy
ISSN:0028-0836, 1476-4687, 1476-4687
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Prompt coronary catheterization and revascularization have markedly improved the outcomes of myocardial infarction, but have also resulted in a growing number of surviving patients with permanent structural damage of the heart, which frequently leads to heart failure. There is an unmet clinical need for treatments for this condition 1 , particularly given the inability of cardiomyocytes to replicate and thereby regenerate the lost contractile tissue 2 . Here we show that expression of human microRNA-199a in infarcted pig hearts can stimulate cardiac repair. One month after myocardial infarction and delivery of this microRNA through an adeno-associated viral vector, treated animals showed marked improvements in both global and regional contractility, increased muscle mass and reduced scar size. These functional and morphological findings correlated with cardiomyocyte de-differentiation and proliferation. However, subsequent persistent and uncontrolled expression of the microRNA resulted in sudden arrhythmic death of most of the treated pigs. Such events were concurrent with myocardial infiltration of proliferating cells displaying a poorly differentiated myoblastic phenotype. These results show that achieving cardiac repair through the stimulation of endogenous cardiomyocyte proliferation is attainable in large mammals, however dosage of this therapy needs to be tightly controlled. MicroRNAs delivered by adeno-associated viral vectors improve global and regional contractility, increase muscle mass and reduce scar size in a porcine model of myocardial infarction.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
Both authors contributed as senior authors
Contributed equally to the work as first authors
ISSN:0028-0836
1476-4687
1476-4687
DOI:10.1038/s41586-019-1191-6