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.
Hammoutene A, Biquard L, Lasselin J, Kheloufi M, Tanguy M, Vion AC, Mérian J, Colnot N, Loyer X, Tedgui A, Codogno P, Lotersztajn S, Paradis V, Boulanger CM, Rautou PE.
J Hepatol. 2019 Nov.
Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome. NAFLDencompasses a spectrum of histological lesions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which includes, in addition to steatosis, hepatocellular injury, inflammation, and varying degree of fibrosis, and can progress to cirrhosis and liver cancer. We recently demonstrated that autophagy is defective in liver endothelial cells of patients with NASH and that this defect is induced by inflammatory mediators present in the portal blood of patients with metabolic syndrome
We also demonstrated that deficiency in autophagy induces liver endothelial cell alterations responsible for liver inflammation, liver cell death and liver fibrosis, thus promoting NASH development .