Details

Autor(en) / Beteiligte

• Smadja, David M
• d'Audigier, Clément
• Bièche, Ivan
• Evrard, Solène
• Mauge, Laetitia
• Dias, Juliana-Vieira
• Labreuche, Julien
• Laurendeau, Ingrid
• Marsac, Bérengère
• Dizier, Blandine
• Wagner-Ballon, Orianne
• Boisson-Vidal, Catherine
• Morandi, Verônica
• Duong-Van-Huyen, Jean-Paul
• Bruneval, Patrick
• Dignat-George, Françoise
• Emmerich, Joseph
• Gaussem, Pascale

Titel

Thrombospondin-1 is a plasmatic marker of peripheral arterial disease that modulates endothelial progenitor cell angiogenic properties

Ist Teil von

• Arteriosclerosis, thrombosis, and vascular biology, 2011-03, Vol.31 (3), p.551-559

Ort / Verlag

United States

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• We 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. Plasma 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. TSP-1 is a potential biomarker of PAD and ECFC-induced angiogenesis, suggesting that TSP-1 modulation might improve local tissue ischemia in this setting. ( NCT00377897.).