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Circulation. 2009 Jun 2;119(21):2808-17. doi: 10.1161/CIRCULATIONAHA.108.816710. Epub 2009 May 18.

Microparticles from ischemic muscle promotes postnatal vasculogenesis.

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  • 1Paris Cardiovascular Research Center, INSERM U, Hôpital Européen Georges Pompidou, Université Paris-Descartes, France.

Abstract

BACKGROUND:

We hypothesized that microparticles (MPs) released after ischemia are endogenous signals leading to postischemic vasculogenesis.

METHODS AND RESULTS:

MPs from mice ischemic hind-limb muscle were detected by electron microscopy 48 hours after unilateral femoral artery ligation as vesicles of 0.1- to 1-microm diameter. After isolation by sequential centrifugation, flow cytometry analyses showed that the annexin V(+) MP concentration was 3.5-fold higher in ischemic calves than control muscles (1392+/-406 versus 394+/-180 annexin V(+) MPs per 1 mg; P<0.001) and came mainly from endothelial cells (71% of MPs are CD(144+)). MPs isolated from ischemic muscles induced more potent in vitro bone marrow-mononuclear cell (BM-MNC) differentiation into cells with endothelial phenotype than those isolated from control muscles. MPs isolated from atherosclerotic plaques were ineffective, whereas those isolated from apoptotic or interleukin-1beta-activated endothelial cells also promoted BM-MNC differentiation. Interestingly, MPs from ischemic muscles produced more reactive oxygen species and expressed significantly higher levels of NADPH oxidase p47 (6-fold; P<0.05) and p67 subunits (16-fold; P<0.001) than controls, whereas gp91 subunit expression was unchanged. BM-MNC differentiation was reduced by 2-fold with MPs isolated from gp91-deficient animals compared with wild-type mice (P<0.05). MP effects on postischemic revascularization were then examined in an ischemic hind-limb model. MPs isolated from ischemic muscles were injected into ischemic legs in parallel with venous injection of BM-MNCs. MPs increased the proangiogenic effect of BM-MNC transplantation, and this effect was blunted by gp91 deficiency. In parallel, BM-MNC proangiogenic potential also was reduced in ABCA1 knockout mice with impaired vesiculation.

CONCLUSIONS:

MPs produced during tissue ischemia stimulate progenitor cell differentiation and subsequently promote postnatal neovascularization.

PMID:
19451354
[PubMed - indexed for MEDLINE]
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