Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization
Alexander Brill1, Olga Dashevsky, Julia Rivo
1Coagulation Unit, Hematology Department, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel. brilla@hadassah.org.il
Objective:
Platelet activation is accompanied by the release of microparticles. However, little is known about the role of platelet-derived microparticles (PMP) in the regulation of angiogenesis and related clinical situations. The aim of our study was to evaluate the effect of PMP on angiogenesis and to analyze its mechanisms.
Methods:
Both in vitro (rat aortic ring model, cell invasion test) and in vivo (agarose bead transplantation, artificial cardiac ischemia in Sabra rats) approaches were used in the study.
Results:
A dose-dependent pro-angiogenic effect of PMP was observed in the rat aortic ring model. This effect could be eliminated by inhibition of VEGF, bFGF, and PDGF, but not heparanase. PMP exerted their effect via PI 3-kinase, Src kinase, and ERK, whereas protein kinase C and p38 were not involved. Moreover, PMP induced invasion of endothelial cells through a layer of matrigel. This effect was mediated by VEGF, heparanase, and PDGF, but not bFGF. Furthermore, PMP induced angiogenesis in an in vivo model in which agarose beads containing PMP were transplanted subcutaneously into mice. In addition, the effect of PMP on angiogenesis was evaluated in the model of in vivo chronic myocardial ischemia in rats. Ischemia induced a decrease in the number of functioning capillaries (34+/-21.5 vs. 157+/-42.0 per view field), but their amount increased after injection of PMP into the myocarium (97+/-27.3; p<0.001 vs. ischemia without PMP).
Conclusions:
PMP induce angiogenesis both in vitro and in vivo. Injection of PMP into the ischemic myocardium might improve the process of revascularization after chronic ischemia.
Insights
Platelet-derived microparticles (PMP) promote new blood vessel growth (angiogenesis) in laboratory models and in animals with heart ischemia. PMP may improve revascularization in ischemic conditions.
Area of Science:
- Cardiovascular Biology
- Cell Biology
- Biomedical Research
Background:
- Platelet activation releases microparticles, but their role in angiogenesis is unclear.
- Platelet-derived microparticles (PMP) are implicated in various physiological and pathological processes.
Purpose of the Study:
- To investigate the effect of PMP on angiogenesis.
- To elucidate the underlying mechanisms of PMP-mediated angiogenesis.
Main Methods:
- In vitro studies: rat aortic ring assay, endothelial cell invasion assays.
- In vivo studies: agarose bead transplantation in mice, artificial cardiac ischemia model in rats.
Main Results:
- PMP demonstrated a dose-dependent pro-angiogenic effect in vitro, mediated by VEGF, PI 3-kinase, Src kinase, and ERK.
- PMP enhanced endothelial cell invasion, involving VEGF, heparanase, and PDGF.
- PMP promoted angiogenesis in vivo and improved capillary function in a rat model of chronic myocardial ischemia.
Conclusions:
- PMP significantly induce angiogenesis both in vitro and in vivo.
- PMP administration may enhance revascularization in ischemic myocardium, suggesting therapeutic potential.
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