USE OF MYELOPEROXIDASE INHIBITORS FOR THE TREATMENT OF CARDIOVASCULAR DISEASES IN PATIENTS SUFFERING FROM MYELOPROLIFERATIVE NEOPLASMS
Arterial cardiovascular events, i.e.the leading cause of death in patients with JAK2V617F myeloproliferative neoplasms (MPN), are poorly understood. The inventors demonstrated that Jak2V617F mice display a strong increase in arterial contraction with disturbed endothelial nitric oxide pathway and increased endothelial oxidative stress. This augmented arterial contraction was reproduced by circulating microvesicles isolated from patients carrying JAK2V617F and by microvesiclesderived fromJAK2V617F erythrocytes. Using proteomics, the inventors identified a high expression of myeloperoxidase in microvesicles derived from JAK2V617F erythrocytes that could account for this effect. The results prompt the inventors to conclude that JAK2V617F MPN induce a potent increase in arterial contraction with increased endothelial oxidative stress, mediated by erythrocytes microvesicles and that myeloperoxidase (MPO) inhibitors would be suitable for preventing cardiovascular diseases in patient suffering from MPN.
- J Clin Invest. 2020 Feb 11. pii: 124566. doi: 10.1172/JCI124566. [Epub ahead of print]