Pharmacological Silencing of MicroRNA-152 Prevents Pressure Overload-Induced Heart Failure.
Animals
Antagomirs
/ administration & dosage
Aorta
/ physiopathology
Case-Control Studies
Disease Models, Animal
Gene Silencing
Glutaredoxins
/ genetics
Heart Failure
/ genetics
Humans
Ligation
Male
Mice, Inbred C57BL
Mice, Transgenic
MicroRNAs
/ genetics
Mitochondria, Heart
/ genetics
Myocytes, Cardiac
/ metabolism
Proof of Concept Study
Stroke Volume
Ventricular Function, Left
heart failure
inflammation
mice
microRNA
phenotype
Journal
Circulation. Heart failure
ISSN: 1941-3297
Titre abrégé: Circ Heart Fail
Pays: United States
ID NLM: 101479941
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
entrez:
13
3
2020
pubmed:
13
3
2020
medline:
18
8
2020
Statut:
ppublish
Résumé
MicroRNAs are small, noncoding RNAs that play a key role in gene expression. Accumulating evidence suggests that aberrant microRNA expression contributes to the heart failure (HF) phenotype; however, the underlying molecular mechanisms are not well understood. A better understanding of the mechanisms of action of microRNAs could potentially lead to targeted therapies that could halt the progression or even reverse HF. We found that microRNA-152 (miR-152) expression was upregulated in the failing human heart and experimental animal models of HF. Transgenic mice with cardiomyocyte-specific miR-152 overexpression developed systolic dysfunction (mean difference, -38.74% [95% CI, -45.73% to -31.74%]; The upregulation of miR-152 expression in the failing myocardium contributes to HF pathophysiology. Preclinical evidence suggests that miR-152 inhibition preserves cardiac function in a model of pressure overload-induced HF. These findings offer new insights into the pathophysiology of HF and point to miR-152-Glrx5 axis as a potential novel therapeutic target.
Sections du résumé
BACKGROUND
MicroRNAs are small, noncoding RNAs that play a key role in gene expression. Accumulating evidence suggests that aberrant microRNA expression contributes to the heart failure (HF) phenotype; however, the underlying molecular mechanisms are not well understood. A better understanding of the mechanisms of action of microRNAs could potentially lead to targeted therapies that could halt the progression or even reverse HF.
METHODS AND RESULTS
We found that microRNA-152 (miR-152) expression was upregulated in the failing human heart and experimental animal models of HF. Transgenic mice with cardiomyocyte-specific miR-152 overexpression developed systolic dysfunction (mean difference, -38.74% [95% CI, -45.73% to -31.74%];
CONCLUSIONS
The upregulation of miR-152 expression in the failing myocardium contributes to HF pathophysiology. Preclinical evidence suggests that miR-152 inhibition preserves cardiac function in a model of pressure overload-induced HF. These findings offer new insights into the pathophysiology of HF and point to miR-152-Glrx5 axis as a potential novel therapeutic target.
Identifiants
pubmed: 32160771
doi: 10.1161/CIRCHEARTFAILURE.119.006298
pmc: PMC7439562
mid: NIHMS1555361
doi:
Substances chimiques
Antagomirs
0
Glrx5 protein, mouse
0
Glutaredoxins
0
MIRN152 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e006298Subventions
Organisme : NHLBI NIH HHS
ID : K99 HL104002
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL104002
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR026780
Pays : United States
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