February 2020

Erythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm

Johanne Poisson, Marion Tanguy, …, Chantal M. Boulanger, Pierre-Emmanuel Rautou
J Clin Invest. 2020. https://doi.org/10.1172/JCI124566

Arterial cardiovascular events are the leading cause of death in patients with JAK2V617F myeloproliferative neoplasms. However, their mechanisms are poorly understood.
In the present study, we observed that genetically modified mice developing JAK2V617F myeloproliferative neoplasms have a strong arterial contraction in response to vasoconstrictors that could account for arterial cardiovascular events observed in patients. We then investigated the mechanisms involved and demonstrated that microvesicles, i.e. cell debris, derived from red blood cells, and circulating in the blood of patients with JAK2V617F myeloproliferative neoplasms transfer a protein (myeloperoxidase) to endothelial cells thus increasing arterial response. We finally showed that treatments, including hydroxyurea and simvastatin, improved arterial response and could thus be attractive to prevent arterial cardiovascular events in patients with JAK2V617F myeloproliferative neoplasms.