Direct implantations of erythropoietin and autologous EPCs in critical limb ischemia (CLI) area restored CLI area blood flow and rescued remote AMI-induced LV dysfunction - 18/09/19
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| Iconographies | 13 |
| Vidéos | 0 |
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Highlights |
• | Inflammatory, apoptotic, fibrotic and DNA-damaged biomarkers markedly increased in ischemia-related organ dysfunction. |
• | EPO-EPC therapy increased soluble angiogenesis factors in both the circulation and ischemia-related organ dysfunction. |
• | Direct implantation of EPO-EPC to quadriceps muscle rescued blood flow and preserved remote heart function in CLI-AMI. |
Abstract |
Background |
This study tested the hypothesis that intramuscular injections of erythropoietin (EPO) and endothelial progenitor cells (EPC) to critical limb ischemia (CLI; primary treatment site) could also improve heart function in rat after acute myocardial infarction (AMI; remote ischemic organ).
Method |
Adult-male SD rats (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (CLI-AMI), group 3 [CLI-AMI + EPO (10 mg/kg)], group 4 [CLI-AMI + EPCs (1.2 × 106)] and group 5 (CLI-AMI + EPCs + EPO).
Results |
By day 21 (end of study period), 2-D echo and Laser doppler showed that left-ventricular injection fraction (LVEF) and the ratio of ischemic to normal blood flow were highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, but not different in the latter two groups (all p < 0.0001). Flow cytometry and ELISA demonstrated that circulating angiogenesis factors were significantly progressively increased from groups 1 to 5 (all p < 0.001). The number of small vessels and protein (CD31/eNOS)/cellular (vWF) expressions reflecting integrity of endothelium exhibited an identical pattern to LVEF whereas protein (VEGF/SDF-1α)/cellular (VEGF) expressions were significantly progressively increased from groups 1 to 5 in quadriceps and heart tissues (all p < 0.0001). Protein expressions of apoptotic (Bax/caspase-3/PARP)/inflammatory (MMP-9) and microscopic findings of ischemic/fibrotic/collagen-deposition areas and DNA-damage marker (γ-H2AX+) were lowest in group 1 and significantly progressively decreased from groups 2 to 5 in quadriceps and heart tissues (all p < 0.0001).
Conclusions |
Direct injection of EPO-EPC into CLI effectively restored blood flow in the CLI area and also preserved remote heart function.
Le texte complet de cet article est disponible en PDF.Keywords : Primary and remote organ damage, Erythropoietin, Endothelial progenitor cell, Angiogenesis
Plan
Vol 118
Article 109296- octobre 2019 Retour au numéro
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