Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization.
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.
Brill
Alexander
A
Coagulation Unit, Hematology Department, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel. brilla@hadassah.org.il
Dashevsky
Olga
O
Rivo
Julia
J
Gozal
Yaacov
Y
Varon
David
D
D000818:Animals; D001011:Aorta; D001792:Blood Platelets / Q000502:physiology*; D002196:Capillaries; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000378:metabolism*; D049329:Nanostructures; D018919:Neovascularization, Physiologic / Q000502:physiology*; D015539:Platelet Activation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology
D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2