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.
BACKGROUND: We hypothesized that microparticles (MPs) released after ischemia are endogenous signals leading to postischemic vasculogenesis. METHODS AND RESULTS: MPs from miceischemic 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 ischemiccalves 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.
Authors: Stéphane M Camus; João A De Moraes; Philippe Bonnin; Paul Abbyad; Sylvain Le Jeune; François Lionnet; Laurent Loufrani; Linda Grimaud; Jean-Christophe Lambry; Dominique Charue; Laurent Kiger; Jean-Marie Renard; Claire Larroque; Hervé Le Clésiau; Alain Tedgui; Patrick Bruneval; Christina Barja-Fidalgo; Antigoni Alexandrou; Pierre-Louis Tharaux; Chantal M Boulanger; Olivier P Blanc-Brude Journal: Blood Date: 2015-03-31 Impact factor: 22.113
Authors: Nadia El Harane; Anaïs Kervadec; Valérie Bellamy; Laetitia Pidial; Hany J Neametalla; Marie-Cécile Perier; Bruna Lima Correa; Léa Thiébault; Nicolas Cagnard; Angéline Duché; Camille Brunaud; Mathilde Lemitre; Jeanne Gauthier; Alexandra T Bourdillon; Marc P Renault; Yeranuhi Hovhannisyan; Solenne Paiva; Alexandre R Colas; Onnik Agbulut; Albert Hagège; Jean-Sébastien Silvestre; Philippe Menasché; Nisa K E Renault Journal: Eur Heart J Date: 2018-05-21 Impact factor: 29.983