Sickle cell disease (SCD) is so called because of the abnormal sickle shape of the red blood cells in individuals with this blood disorder. The abnormal shape of the red blood cells prevents them passing easily through blood vessels, which can become obstructed such that blood flow to an organ is restricted, causing pain and organ damage. An episode of blood vessel obstruction is known as a vaso-occlusive crisis (VOC) and a new study, performed by Pierre-Louis Tharaux and colleagues, at INSERM U689, France, has indicated that a drug known as bosentan prevents experimentally induced VOC in a mouse model of SCD.
In vivo analysis indicated that during experimentally induced VOC, blood vessel resistance was increased through a process mediated by the protein endothelin. As bosentan, which is used to treat individuals with pulmonary arterial hypertension, is a drug that acts as an antagonist of both endothelin receptors, the authors assessed its ability to treat experimentally induced VOC in a mouse model of SCD. The drug was found to have many beneficial effects that cumulated to prevent the death of the mice, leading to the suggestion that bosentan might provide a new way to limit VOC, and thereby organ damage, in individuals with SCD.
TITLE: Endothelin receptor antagonism prevents hypoxia-induced mortality and morbitity in a mouse model of sickle-cell disease
AUTHOR CONTACT:
Pierre-Louis Tharaux
INSERM U689, Paris, France.
Phone: 33-615-95-53-67; Fax: 33-14-81-31-28; E-mail: tharaux@chusa.jussieu.fr .
View the PDF of this article at: https://www.the-jci.org/article.php?id=33308
Journal of Clinical Investigation