AUTHOR=Theofilis Panagiotis , Vogiatzi Georgia , Oikonomou Evangelos , Gazouli Maria , Siasos Gerasimos , Katifelis Hector , Perrea Despoina , Vavuranakis Manolis , Iliopoulos Dimitrios C , Tsioufis Costas , Tousoulis Dimitris 

TITLE=The Effect of MicroRNA-126 Mimic Administration on Vascular Perfusion Recovery in an Animal Model of Hind Limb Ischemia

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.724465

DOI=10.3389/fmolb.2021.724465

ISSN=2296-889X

ABSTRACT=<p><bold>Background:</bold> MicroRNAs have been linked to angiogenesis and could prove to be valuable future therapeutic targets in ischemic cardiovascular diseases.</p><p><bold>Methods:</bold> Ten-week-old male C57Bl/6 mice were subjected to left femoral artery ligation and were treated with microRNA-126 mimic at a dose of 5 mg/kg (Group A, <italic>n</italic> = 10) or 5 mg/kg microRNA mimic negative control (Group B, <italic>n</italic> = 10) on days 1, 3, and 7. Laser Doppler imaging was performed to verify successful ligation on day 0 and to evaluate differences in the ischemic-to-normal (I/N) hind limb perfusion ratio on day 28. Muscle tissue expression of microRNA-126 and vascular endothelial growth factor (VEGF) was determined <italic>via</italic> PCR.</p><p><bold>Results:</bold> Following microRNA-126 mimic administration in Group A subjects, we noted a stepwise increase in I/N hind limb perfusion ratio (Day 0: 0.364 ± 0.032 vs. Day 8: 0.788 ± 0.049 vs. Day 28: 0.750 ± 0.039, <italic>p</italic> = 0.001). In Group B a stepwise increase in I/N hind limb perfusion ratio was observed (Day 0: 0.272 ± 0.057 vs. Day 8: 0.382 ± 0.020 vs. Day 28: 0.542 ± 0.028, <italic>p</italic> = 0.074). Muscle tissue expression of microRNA-126 in the ischemic hind limb of Group A was 350-fold lower compared to the ischemic hind limb of Group B (<italic>p</italic> &lt; 0.001). A higher expression (14.2-fold) of VEGF in the ischemic hind limb of microRNA-126-treated mice compared to that of control group was detected (<italic>p</italic> &lt; 0.001). A statistically significant negative correlation was noted between microRNA-126 and VEGF tissue expression levels in the ischemic limbs of the entire study population.</p><p><bold>Conclusion:</bold> MicroRNA-126 delivery in the ischemic hind limb of mice improved vascular perfusion with VEGF upregulation.</p>