The impact of proangiogenic microRNA modulation on blood flow recovery following hind limb ischemia. A systematic review and meta-analysis of animal studies

2021 ◽  
pp. 106906
Author(s):  
Panagiotis Theofilis ◽  
Evangelos Oikonomou ◽  
Georgia Vogiatzi ◽  
Alexios S. Antonopoulos ◽  
Gerasimos Siasos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Blood Flow ◽  
Hind Limb ◽  
Animal Studies ◽  
Meta Analysis ◽  
Limb Ischemia ◽  
Hind Limb Ischemia ◽  
The Impact

Outgrowing Endothelial Cells That Are Derived from Human Umbilical Cord Blood Improve Neovascularization in Hind-Limb Ischemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3697-3697
Author(s):  
Eun-Sun Yoo ◽  
KiHwan Kwon ◽  
Jee-Young Ahn ◽  
Soo-Ah Oh ◽  
Hye-Jung Chang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cord Blood ◽  
Umbilical Cord Blood ◽  
Hind Limb ◽  
Limb Ischemia ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Hind Limb Ischemia

Abstract Backgroud: Human umbilical cord blood (UCB) contains a high number of endothelial progenitor cells (EPCs) and may be useful for the treatment of ischemic disease. Recently, we have isolated EPCs from UCB having different biologic properties for angiogenic capabilities in vitro. In this present study, the aim is to examine the usefulness of OECs in hind-limb ischemia. Methods: Mononuclear cells from UCB cultured using EGM-2 medium with VEGF, IGF-1 and FGF for 21 days. Early spindle-shaped cells (early OECs), which were grown during the first week of culture and late cobblestone shaped cells (late OECs), which were in peak growth during the third week of culture were found. The hind-limb ischemia was established as follows: Athymic nude mice (BALB/C-nu) 18–22 g in weight were anesthetized with pentobarbital (60 mg/kg) and their left femoral arteries and main extension arteries were operatively resected. To examine the effect of the vasculogenesis of the two types of OECs, the mice were divided into three groups (PBS, early and late OECs). Twenty-four hours after operative excision 5 × 105 OECs in 200 μl and an equal volume of PBS were administered by intramuscular injection into the mice on hind-limb ischemia. To compare the effect of OECs on neovascularization in vivo, the analysis of blood flow of ischemic and healthy hind limbs was performed on days 1 and 21 after surgery using near-infrared (NIR) imaging with incocyanne Green (ICG). Results: Late OECs expressed a high level of mRNA on endothelial marker genes and formed capillary tubes in Matrigel plates. The early spindle cells excreted more angiogenic cytokines and had more migratory ability. We divided the mice into two groups according to the degree of perfusion; good (22.5–50%/min) and poor (0–22.5%) perfusion. OECs improved the blood flow of the ischemic hind-limb in the ’good’ perfusion group but not in the ’poor’ perfusion group. Early OECs led to a more significant improvement in blood flow than that of the late OECs. Conclusion: The different types of OECs from UCB have different biologic properties in vitro and different vasculogenic potential in vivo as well. The results might have potential application for the treatment of hind-limb ischemia.

Placenta-derived PLX-PAD mesenchymal-like stromal cells are efficacious in rescuing blood flow in hind limb ischemia mouse model by a dose- and site-dependent mechanism of action

Cytotherapy ◽  
2017 ◽  
Vol 19 (12) ◽  
pp. 1438-1446 ◽  
Author(s):  
Efrat Zahavi-Goldstein ◽  
Michal Blumenfeld ◽  
Dana Fuchs-Telem ◽  
Lena Pinzur ◽  
Shy Rubin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Mouse Model ◽  
Mechanism Of Action ◽  
Stromal Cells ◽  
Hind Limb ◽  
Limb Ischemia ◽  
Hind Limb Ischemia ◽  
Dependent Mechanism

scholarly journals Effects on duration of post-operative ischemia and patterns of blood flow recovery in different conditions of mouse hind limb ischemia

Vascular Cell ◽  
2011 ◽  
Vol 3 (1) ◽  
pp. 14 ◽  
Author(s):  
Husain A Al-Mubarak ◽  
Talal M Alamri ◽  
Saif A Aljabab ◽  
Mohammad Atteya ◽  
Adrian Quan ◽  
...  
Keyword(s):  
Blood Flow ◽  
Hind Limb ◽  
Limb Ischemia ◽  
Hind Limb Ischemia

Abstract 456: Rage Suppresses Angiogenesis and Blood Flow Recovery After Hind Limb Ischemia in Diabetic Mice Through Modulation of Macrophage Inflammation and Macrophage-endothelial Interactions

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Raquel Lopez Diez ◽  
Qing Li ◽  
Huilin Li ◽  
Shi Fang Yan ◽  
Ann Marie Schmidt
Keyword(s):  
Blood Flow ◽  
Hind Limb ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Limb Ischemia ◽  
Diabetic Mice ◽  
Hind Limb Ischemia ◽  
Inflammatory Monocytes ◽  
Baseline Levels ◽  
Ischemic Muscle

Peripheral vascular disease is a condition characterized by atherosclerotic narrowed arteries distal to the aorta which triggers an acute or critical limb ischemia. Development of ischemic PVD has been considered one of the principal complications of diabetes, leading to amputation of digits and limbs. Advanced glycation end products (AGE) ligands and their receptor (RAGE) have been implicated in multiple key mechanisms underlying diabetes and diabetic complications, including hypoxia and ischemia/reperfusion injury. We tested the hypothesis that vascular recovery after hind limb ischemia would be rescued by deficiency of RAGE, at least in part through modulation of macrophage dysfunction. Wild type (WT) and Ager deficient mice were rendered diabetic with streptozotocin, and subjected to unilateral hind limb ischemia. Previous results showed an increased accumulation and expression of AGEs and RAGE in ischemic muscle, especially in diabetic WT mice. Attenuated angiogenesis and impaired blood flow recovery were also observed, in parallel with reduced early inflammatory macrophage infiltration into ischemic muscle in the WT diabetic mice. We performed flow cytometry to analyze circulating monocyte subsets: pro-inflammatory Ly6G/C hi and anti-inflammatory Ly6G/C lo . Work by others reported higher levels of monocytes in diabetes in the baseline state without injury; our data indicate that the increase is mostly attributed to the pro-inflammatory Ly6G/C hi population, being significantly lower in the Ager -/- diabetic mice. After seven days of ischemia to the unilateral hind limb, lower levels of circulating pro-inflammatory Ly6G/C hi monocytes were found in both WT and Ager deficient diabetic mice. After four weeks of injury, the pro-inflammatory monocytes levels were significantly recovered to baseline levels in Ager -/- mice, whereas WT mice failed to reacquire their baseline levels. In vitro studies using murine endothelial cells and murine macrophages revealed that RAGE suppressed macrophage-endothelial cell interaction, particularly in diabetes-relevant concentrations of D-glucose. These data suggest unique ischemia-dependent mechanisms in hind limb ischemia through RAGE down-regulation of the early adaptive immune response.

scholarly journals Adiponectin Fails in Improving Angiogenic Repair in Streptozocin-Treated or Leprdb/db Mice after Hind Limb Ischemia

2012 ◽  
Vol 2012 ◽  
pp. 1-10
Author(s):  
Kurt Belisle ◽  
Martin Andrassy ◽  
Jochen Schneider ◽  
Stephan Schiekofer
Keyword(s):  
Blood Flow ◽  
Hind Limb ◽  
Limb Ischemia ◽  
Dominant Negative ◽  
Laser Doppler ◽  
Hind Limb Ischemia ◽  
Tissue Ischemia ◽  
Glucose Levels ◽  
Elevated Glucose

Objectives. Type 1 and 2 diabetes carry risk factors for the development of microvascular diseases with associated impairment of angiogenic repair. Here, we investigated whether adiponectin, an adipocyte-specific adipocytokine with antiatherosclerotic and antidiabetic properties, regulates angiogenic repair in response to tissue ischemia in Leprdb/db and streptozocin-treated diabetic mouse models. Methods. Adenoviral vectors containing the gene for β-galactosidase, full-length mouse adiponectin, and dominant-negative AMPKα2 were used in streptozocin-treated male Leprdb/db mice, after which hind limb blood flow was measured using a laser doppler blood flow analyzer. Results. The angiogenic repair of ischemic hind limbs was impaired in both streptozocin-treated and Leprdb/db mice compared to wild-type mice as evaluated by laser doppler flow and capillary density analyses. Adenovirus-mediated administration of adiponectin accelerated angiogenic repair after hind limb ischemia in WT mice, but not in Leprdb/db mice or mice treated with streptozocin. In vitro experiments using HUVECs highlighted the antiapoptotic and proangiogenic properties of adiponectin but could not demonstrate accelerated differentiation of endothelial cells into tube-like structures at elevated glucose levels. Conclusions. External administration of adiponectin at elevated glucose levels may not be useful in the treatment of diabetes mellitus-related vascular deficiency diseases.

scholarly journals Pericyte-Specific Ninjurin1 Deletion Attenuates Vessel Maturation and Blood Flow Recovery in Hind Limb Ischemia

2018 ◽  
Vol 38 (10) ◽  
pp. 2358-2370 ◽  
Author(s):  
Akiho Minoshima ◽  
Maki Kabara ◽  
Motoki Matsuki ◽  
Yuri Yoshida ◽  
Kohei Kano ◽  
...  
Keyword(s):  
Blood Flow ◽  
Hind Limb ◽  
Limb Ischemia ◽  
Hind Limb Ischemia ◽  
Vessel Maturation

scholarly journals Effect of Endothelin Receptor Antagonists on Clinically Relevant Outcomes after Experimental Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

2015 ◽  
Vol 35 (7) ◽  
pp. 1085-1089 ◽  
Author(s):  
Kamil G Laban ◽  
Mervyn DI Vergouwen ◽  
Rick M Dijkhuizen ◽  
Emily S Sena ◽  
Malcolm R Macleod ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Animal Studies ◽  
Meta Analysis ◽  
Case Fatality ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor

In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.

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