Overexpression of miR-210 and its significance in ischemic tissue damage

G. Zaccagnini, B. Maimone, P. Fuschi, D. Maselli, G. Spinetti, C. Gaetano, F. Martelli

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Hypoxia-induced miR-210 displays a pro-survival, cytoprotective and pro-angiogenic role in several in vitro systems. In vivo, we previously found that miR-210 inhibition increases ischemic damage. Here we describe the generation of a versatile transgenic mouse model allowing the evaluation of miR-210 therapeutic potential in ischemic cardiovascular diseases. We generated a Tet-On miR-210 transgenic mouse strain (TG-210) by targeted transgenesis in the ROSA26 locus. To functionally validate miR-210 transgenic mice, hindlimb ischemia was induced by femoral artery dissection. Blood perfusion was evaluated by power Doppler while tissue damage and inflammation were assessed by histological evaluation. We found that miR-210 levels were rapidly increased in TG-210 mice upon doxycycline administration. miR-210 overexpression was maintained over time and remained within physiological levels in multiple tissues. When hindlimb ischemia was induced, miR-210 overexpression protected from both muscular and vascular ischemic damage, decreased inflammatory cells density and allowed to maintain a better calf perfusion. In conclusion, we generated and functionally validated a miR-210 transgenic mouse model. Albeit validated in the context of a specific cardiovascular ischemic disease, miR-210 transgenic mice may also represent a useful model to assess the function of miR-210 in other physio-pathological conditions.

Original languageEnglish
Article number9563
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Transgenic Mice
Hindlimb
Cardiovascular Diseases
Ischemia
Perfusion
Gene Transfer Techniques
Doxycycline
Femoral Artery
Blood Vessels
Dissection
Cell Count
Inflammation
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Overexpression of miR-210 and its significance in ischemic tissue damage. / Zaccagnini, G.; Maimone, B.; Fuschi, P.; Maselli, D.; Spinetti, G.; Gaetano, C.; Martelli, F.

In: Scientific Reports, Vol. 7, No. 1, 9563, 01.12.2017.

Research output: Contribution to journalArticle

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