During exposure to ischemia-reperfusion (I/R) insult, angiotensin II (AngII)-induced endothelin-1 (ET-1) upregulation in endothelial cells progressively impairs nitric oxide (NO) bioavailability while increasing levels of superoxide anion (O2-) and leading to the onset of endothelial dysfunction. Moreover, the overexpression of ET-1 increases the endothelial and circulating levels of von Willebrand factor (vWF), a glycoprotein with a crucial role in arterial thrombus formation. Nowadays, the non-hemostatic role of endothelial vWF is emerging, although we do not yet know whether its increased expression is cause or consequence of endothelial dysfunction. Notably, the vWF blockade or depletion leads to endothelial protection in cultured cells, animal models of vascular injury, and patients as well. Despite the recent efforts to develop an effective pharmacological strategy, the onset of endothelial dysfunction is still difficult to prevent and remains closely related to adverse clinical outcome. Unraveling the non-hemostatic role of endothelial vWF in the onset of endothelial dysfunction could provide new avenues for protection against vascular injury mediated by AngII.

New insights into the non-hemostatic role of von Willebrand Factor in endothelial protection

AGOSTINI, Silvia;LIONETTI, Vincenzo
2017-01-01

Abstract

During exposure to ischemia-reperfusion (I/R) insult, angiotensin II (AngII)-induced endothelin-1 (ET-1) upregulation in endothelial cells progressively impairs nitric oxide (NO) bioavailability while increasing levels of superoxide anion (O2-) and leading to the onset of endothelial dysfunction. Moreover, the overexpression of ET-1 increases the endothelial and circulating levels of von Willebrand factor (vWF), a glycoprotein with a crucial role in arterial thrombus formation. Nowadays, the non-hemostatic role of endothelial vWF is emerging, although we do not yet know whether its increased expression is cause or consequence of endothelial dysfunction. Notably, the vWF blockade or depletion leads to endothelial protection in cultured cells, animal models of vascular injury, and patients as well. Despite the recent efforts to develop an effective pharmacological strategy, the onset of endothelial dysfunction is still difficult to prevent and remains closely related to adverse clinical outcome. Unraveling the non-hemostatic role of endothelial vWF in the onset of endothelial dysfunction could provide new avenues for protection against vascular injury mediated by AngII.
2017
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11382/513611
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 13
social impact