Dissertation committee:
Ηλιόπουλος Δημήτριος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τούσουλης Δημήτρης, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σιάσος Γεράσιμος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τσιούφης Κωνσταντίνος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Βλαχόπουλος Χαράλαμπος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αγγουράς Δημήτριος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αγγέλη Κωνσταντίνα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Background
MicroRNAs (miRs) have been linked to angiogenesis and could prove to be valuable future therapeutic targets in ischemic cardiovascular diseases.
Aims
We investigated the speculated pro-angiogenic effect of miR-126 through administration of a mimic analogue in an in vivo model of hind limb ischemia.
Methods
Ten-week-old male C57BL/6 mice were subjected to left femoral artery ligation and were treated with miR-126 mimic at a dose of 5 mg/kg (Group A, n=10) or 5 mg/kg miR mimic negative control (Group B, n=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 miR-126 and vascular endothelial growth factor (VEGF) was determined via PCR.
Results
Following miR-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, p=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, p=0.074). Muscle tissue expression of miR-126 in the ischemic hind limb of Group A was 350-fold lower compared to the ischemic hind limb of Group B (p<0.001). A higher expression (14.2-fold) of VEGF in the ischemic hind limb of miR-126-treated mice compared to that of control group was detected (p<0.001). A statistically significant negative correlation was noted between miR-126 and VEGF tissue expression levels in the ischemic limbs of the entire study population.
Conclusion
MiR-126 delivery in the ischemic hind limb of mice improved vascular perfusion with VEGF upregulation.
Keywords:
Peripheral artery disease, Limb ischemia, Treatment, MicroRNA, Angiogenesis
