• David M Smadja, Clément d'Audigier, Ivan Bièche, Solène Evrard, Laetitia Mauge, Juliana-Vieira Dias, Julien Labreuche, Ingrid Laurendeau, Bérengère Marsac, Blandine Dizier, Orianne Wagner-Ballon, Catherine Boisson-Vidal, Verônica Morandi, Jean-Paul Duong-Van-Huyen, Patrick Bruneval, Françoise Dignat-George, Joseph Emmerich, and Pascale Gaussem.
• Université Paris Descartes, Paris, France. david.smadja@egp.aphp.fr
• Arterioscler. Thromb. Vasc. Biol. 2011 Mar 1; 31 (3): 551-9.

ObjectiveWe examined whether plasma levels of angiogenic factors are altered in plasma of patients with peripheral arterial disease (PAD) and whether these factors affect endothelial progenitor cell-induced angiogenesis.Methods And ResultsPlasma was collected from 184 patients with PAD and 330 age-matched healthy controls. Vascular endothelial growth factor and placental growth factor concentrations did not differ between the groups, whereas we found a linear correlation between PAD disease and thrombospondin (TSP)-1 plasma level. TSP-1 was expressed in newly formed vessels in PAD patients having received local injections of bone marrow mononuclear cells. To analyze the functional role of TSP-1 during neoangiogenesis, we used a Matrigel-plug assay and showed that vascularization of implanted Matrigel-plugs was increased in TSP-1(-/-) mice. Moreover, injections of TSP-1 in C57Bl6/J mice after hindlimb ischemia induced a significant decrease of blood flow recovery. To investigate the effects of TSP-1 on human endothelial colony-forming cell (ECFC) angiogenic potential, recombinant human TSP-1 and a small interfering RNA were used. In vitro, TSP-1 N-terminal part significantly enhanced ECFC adhesion, whereas recombinant human TSP-1 had a negative effect on ECFC angiogenic potential. This effect, mediated by CD47 binding, modulated stromal cell-derived factor 1/CXC chemokine receptor 4 pathway.ConclusionsTSP-1 is a potential biomarker of PAD and ECFC-induced angiogenesis, suggesting that TSP-1 modulation might improve local tissue ischemia in this setting. (Clinical Trial RegistrationNCT00377897.).

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