Copyright © 2005, European Society of Cardiology
Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization
aCoagulation Unit, Hematology Department, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
bAnesthesiology and Critical Care Medicine Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel
* Corresponding author. Tel.: +972 2 6776756; fax: +972 2 6449580. Email address: brilla{at}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.
KEYWORDS Angiogenesis; Platelets; Ischemia
1 First and second authors contributed equally to this study.
Time for primary review 20 days
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