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Tissue plasminogen activator enhances mobilization of endothelial progenitor cells and angiogenesis in murine limb ischemia
- Source :
- International Journal of Cardiology. 168:226-236
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- It has been reported that plasmin induces migration of endothelial cells. We hypothesized that tissue plasminogen activator (tPA) enhanced endothelial progenitor cell (EPC) mobilization from bone marrow (BM) into the circulation and angiogenesis in murine critical limb ischemia (CLI).Forty male B6 mice were randomly divided into group 1 (control), group 2 [control+recombinant tPA (intra-venous 4 mg/kg)], group 3 (CLI) and group 4 (CLI+tPA).The results demonstrated higher MMP-9 activity in BM and circulatory SDF-1α level in groups 2 and 3 than in group 1, and highest in group 4 (all p0.01) at 18 h after CLI. Compared with circulation, SDF-1α level in BM showed an opposite trend (all p0.03). The circulating EPC (C-kit/CD31, Sca-1/KDR, CXCR4/CD34) levels at 18 h after CLI were higher in group 2 than in groups 1 and 3, and highest in group 4 (all p0.03). EPC (C-kit/CD31, Sca-1/KDR) levels in BM were lower in group 1 than in groups 2 to 4 (all p0.03), whereas number of CXCR4/CD34-positive EPCs in BM did not differ among the four groups at 18 h after CLI. Protein expressions of SDF-1α, CXCR4, eNOS, and VEGF, numbers of CD31+, CXCR4+, SDF-1α+, and vWF+ cells through immunofluorescent staining, numbers of small vessels (15 μm) and blood flow measured by Laser Doppler in an ischemic area were significantly higher in group 4 than in group 3 (all p0.005) at day 14 after CLI.tPA treatment enhanced number of circulating EPCs, angiogenesis, and blood flow to ischemic tissue in a murine model of limb ischemia.
- Subjects :
- Male
medicine.medical_specialty
Angiogenesis
Plasmin
Neovascularization, Physiologic
Tissue plasminogen activator
Endothelial progenitor cell
Mice
Random Allocation
Cell Movement
Ischemia
Internal medicine
medicine
Animals
Progenitor cell
Mice, Inbred BALB C
business.industry
Stem Cells
Endothelial Cells
Critical limb ischemia
Hindlimb
body regions
Endocrinology
medicine.anatomical_structure
Tissue Plasminogen Activator
Immunology
Circulatory system
Bone marrow
medicine.symptom
Cardiology and Cardiovascular Medicine
business
medicine.drug
Subjects
Details
- ISSN :
- 01675273
- Volume :
- 168
- Database :
- OpenAIRE
- Journal :
- International Journal of Cardiology
- Accession number :
- edsair.doi.dedup.....1e71b5c969d8cf3d2cd85485f2d9eefe