Local inhibition of microRNA-24 improves reparative angiogenesis and left ventricle remodeling and function in mice with myocardial infarction

Marco Meloni, Micol Marchetti, Kathryn Garner, Ben Littlejohns, Graciela Sala-Newby, Natasa Xenophontos, Ilaria Floris, M. Saadeh Suleiman, Paolo Madeddu, Andrea Caporali, Costanza Emanueli

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Myocardial infarction (MI) is the leading cause of death worldwide. MicroRNAs regulate the expression of their target genes, thus mediating a plethora of pathophysiological functions. Recently, miRNA-24 emerged as an important but controversial miRNA involved in post-MI responses. Here, we aimed at clarifying the effect of adenovirus-mediate intra-myocardial delivery of a decoy for miRNA-24 in a mouse MI model and to investigate the impact of miRNA-24 inhibition on angiogenesis and cardiovascular apoptosis. After MI induction, miRNA-24 expression was lower in the peri-infarct tissue and its resident cardiomyocytes and fibroblasts; while it increased in endothelial cells (ECs). Local adenovirus-mediated miRNA-24 decoy delivery increased angiogenesis and blood perfusion in the peri-infarct myocardium, reduced infarct size, induced fibroblast apopotosis and overall improved cardiac function. Notwithstanding these beneficial effects, miRNA-24 decoy increased cardiomyocytes apoptosis. In vitro, miRNA-24 inhibition enhanced ECs survival, proliferation and networking in capillary-like tubes and induced cardiomyocyte and fibroblast apoptosis. Finally, we identified eNOS as a novel direct target of miR-24 in human cultured ECs and in vivo. Our findings suggest that miRNA-24 inhibition exerts distinct biological effects on ECs, cardiomyocytes and fibroblasts. The overall result of post-infarction local miRNA-24 inhibition appears to be therapeutic.

Original languageEnglish
Pages (from-to)1390-1402
Number of pages13
JournalMolecular Therapy
Volume21
Issue number7
DOIs
Publication statusPublished - Jul 2013

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Ventricular Remodeling
MicroRNAs
Myocardial Infarction
Cardiac Myocytes
Endothelial Cells
Fibroblasts
Apoptosis
Adenoviridae
Infarction
Cause of Death
Cultured Cells
Cell Survival
Myocardium
Perfusion
Cell Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Meloni, M., Marchetti, M., Garner, K., Littlejohns, B., Sala-Newby, G., Xenophontos, N., ... Emanueli, C. (2013). Local inhibition of microRNA-24 improves reparative angiogenesis and left ventricle remodeling and function in mice with myocardial infarction. Molecular Therapy, 21(7), 1390-1402. https://doi.org/10.1038/mt.2013.89

Local inhibition of microRNA-24 improves reparative angiogenesis and left ventricle remodeling and function in mice with myocardial infarction. / Meloni, Marco; Marchetti, Micol; Garner, Kathryn; Littlejohns, Ben; Sala-Newby, Graciela; Xenophontos, Natasa; Floris, Ilaria; Suleiman, M. Saadeh; Madeddu, Paolo; Caporali, Andrea; Emanueli, Costanza.

In: Molecular Therapy, Vol. 21, No. 7, 07.2013, p. 1390-1402.

Research output: Contribution to journalArticle

Meloni, M, Marchetti, M, Garner, K, Littlejohns, B, Sala-Newby, G, Xenophontos, N, Floris, I, Suleiman, MS, Madeddu, P, Caporali, A & Emanueli, C 2013, 'Local inhibition of microRNA-24 improves reparative angiogenesis and left ventricle remodeling and function in mice with myocardial infarction', Molecular Therapy, vol. 21, no. 7, pp. 1390-1402. https://doi.org/10.1038/mt.2013.89
Meloni, Marco ; Marchetti, Micol ; Garner, Kathryn ; Littlejohns, Ben ; Sala-Newby, Graciela ; Xenophontos, Natasa ; Floris, Ilaria ; Suleiman, M. Saadeh ; Madeddu, Paolo ; Caporali, Andrea ; Emanueli, Costanza. / Local inhibition of microRNA-24 improves reparative angiogenesis and left ventricle remodeling and function in mice with myocardial infarction. In: Molecular Therapy. 2013 ; Vol. 21, No. 7. pp. 1390-1402.
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