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Inhibition of miR-92a increases endothelial proliferation and migration in vitro as well as reduces neointimal proliferation in vivo after vascular injury

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Abstract

The role of miR-92a on vascular remodelling after injury is currently unknown. Thus, the aim of the present study was to evaluate the role of miR-92a on rat endothelial and vascular smooth muscle cells proliferation and migration in vitro as well as after balloon injury or arterial stenting in vivo. MiR-92a was highly expressed in RAO-ECs and vascular endothelium, but not in RAO-SMCs or medial smooth muscle as assessed by real-time RT-PCR. Importantly, BrdU incorporation and wound healing assay provide evidence that functional inhibition of miR-92a resulted in an increased RAO-ECs proliferation and migration, but had no effect on RAO-SMCs proliferation or migration in vitro. Immunoblotting analysis revealed an increased phosphorylation of ERK1/2, JNK/SAPK as well as eNOS and phospho-eNOS increased expression level in RAO-ECs as a consequence of miR-92a inhibition. Using gain and loss of function experiments, we showed that miR-92a modulates regulation of KLF4 and MKK4 expression level in endothelial cells. Finally, in vivo administration of antagomiR-92a significantly enhanced re-endothelialization in injured carotid arteries and reduced neointimal formation after balloon injury or arterial stenting. These data provide the first evidence that inhibition of miR-92a may represent a novel strategy to improve endothelial regeneration and reduce restenosis after vascular injury.

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Acknowledgments

This manuscript was dedicated to the memory of Massimo Chiariello, MD. This work was supported by the Italian Ministry of Health (Ricerca Finalizzata 2007, APICE Project) and Cardiovascular Research Association (Genecor).

Conflict of interest

None declared.

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Authors and Affiliations

  1. Laboratory of Molecular and Cellular Cardiology, Cardiovascular Institute, Magna Graecia University, URT - National Research Council, Catanzaro, Italy

    Claudio Iaconetti, Alberto Polimeni, Sabato Sorrentino, Jolanda Sabatino, Antonio Curcio & Ciro Indolfi

  2. Division of Cardiology, Federico II University, Naples, Italy

    Gianluigi Pironti & Giovanni Esposito

  3. Division of Cardiology, Department of Medical and Surgical Sciences, URT - National Research Council, Magna Graecia University, Campus “S. Venuta”, Viale Europa-Germaneto, 88100, Catanzaro, Italy

    Ciro Indolfi

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  1. Claudio Iaconetti
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  2. Alberto Polimeni
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  3. Sabato Sorrentino
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  4. Jolanda Sabatino
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  5. Gianluigi Pironti
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Correspondence to Ciro Indolfi.

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C. Iaconetti and A. Polimeni have contributed equally to this manuscript.

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Iaconetti, C., Polimeni, A., Sorrentino, S. et al. Inhibition of miR-92a increases endothelial proliferation and migration in vitro as well as reduces neointimal proliferation in vivo after vascular injury. Basic Res Cardiol 107, 296 (2012). https://doi.org/10.1007/s00395-012-0296-y

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  • DOI: https://doi.org/10.1007/s00395-012-0296-y

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