Purpose: Anticoagulants are used to reduce complications after acute coronary syndrome. The effects of these drugs on angiogenesis and vasculogenesis, with an important role in plaque destabilization, are not known. Our aim was to test the effect of Bemiparin (B), the low molecular weight heparin with the lowest MW (3600 Da) and the highest anti-FXa/anti-FIIa activity ratio (8:1), and of the synthetic pentasaccharide Fondaparinux (F), a FXa inhibitor, on vasculogenesis and angiogenesis, mediated by endothelial progenitor cells (EPC) and mature endothelial cells (HUVEC), as compared to unfractionated heparin (UFH). Methods: HUVEC or EPC were treated for 24 h with B (0.01-5 I.U./ml), UFH (0.01-5 I.U./ml) or F (0.0005-0.05 mg/ml) before assay for cell viability (MTS), proliferation (BrdU) and in vitro angiogenesis (matrigel) and vasculogenesis (EPC incorporation on matrigel). Drug doses were chosen as the ones used in clinical practice. For angiogenesis, HUVEC were detached and seeded on matrigel. After 20 h, tubule network was quantified. For vasculogenesis, EPC were detached, stained with DiI and seeded on matrigel together with HUVEC. Incorporation of EPC in the tubules was quantified after 20 h. Results: Viability was significantly reduced by the three anticoagulants only at the highest concentration...
Beyond the anticoagulant activity: different effect of glyco-anticoagulants and oligosaccharides on angiogenesis and vasculogenesis
DI STEFANO, ROSSELLA;DA POZZO, ELEONORA;MARTINI, CLAUDIA;BALBARINI, ALBERTO
2009-01-01
Abstract
Purpose: Anticoagulants are used to reduce complications after acute coronary syndrome. The effects of these drugs on angiogenesis and vasculogenesis, with an important role in plaque destabilization, are not known. Our aim was to test the effect of Bemiparin (B), the low molecular weight heparin with the lowest MW (3600 Da) and the highest anti-FXa/anti-FIIa activity ratio (8:1), and of the synthetic pentasaccharide Fondaparinux (F), a FXa inhibitor, on vasculogenesis and angiogenesis, mediated by endothelial progenitor cells (EPC) and mature endothelial cells (HUVEC), as compared to unfractionated heparin (UFH). Methods: HUVEC or EPC were treated for 24 h with B (0.01-5 I.U./ml), UFH (0.01-5 I.U./ml) or F (0.0005-0.05 mg/ml) before assay for cell viability (MTS), proliferation (BrdU) and in vitro angiogenesis (matrigel) and vasculogenesis (EPC incorporation on matrigel). Drug doses were chosen as the ones used in clinical practice. For angiogenesis, HUVEC were detached and seeded on matrigel. After 20 h, tubule network was quantified. For vasculogenesis, EPC were detached, stained with DiI and seeded on matrigel together with HUVEC. Incorporation of EPC in the tubules was quantified after 20 h. Results: Viability was significantly reduced by the three anticoagulants only at the highest concentration...I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
