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Cardiovascular diseases are an increasing social and economical burden. An initial step is the loss of vasculo-protective functions of the endothelium. Therefore, we need to decipher the mechanisms regulating endothelial dysfunctions to identify new therapeutic targets in vascular diseases. In addition, early detection of dysfunctional endothelial cells will help stratify cardiovascular risk and pharmacological treatment of asymptomatic subjects.

In the past decade we have pioneered research on the release of extracellular vesicles (microparticles/ microvesicles or exosomes) from dysfunctional endothelial cells. In particular, we tested the hypothesis that specific changes in circulating extracellular vesicles represent a signature of vascular dysfunction and that vesicle content determines their functional effects during disease progression or repair mechanisms.

The team’s current research addresses the regulation of micro-RNA packaging in extracellular vesicles and their paracrine effects on the development of cardiovascular diseases. We also investigate the vascular impact of circulating microvesicles loaded with hemoglobin, heme and their degradation products in the context of chronic anemic diseases, diabetes and obesity. Recently we have extended our research on endothelial activation, induced by microparticles or other mechanisms, to include the potential role of endothelial autophagy in the development of atherosclerosis (Inserm press release, sept. 2017). Finally, our basic research is complemented by translational activities in clinical studies in association with Paris Hospitals.

See: Circulation Research Leaders in Cardiovascular Science 2017: Chantal M. Boulanger “Exploring the Endothelium”




PARCC_team 01_OK_image réduite2Micro-poétique©Iglika Christova 2018

  • Publications

    Erythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm.

    Arterial cardiovascular events are the leading cause of death in patients with JAK2V617F myeloproliferative neoplasms (MPN). However, their mechanisms are poorly understood. The high prevalence of myocardial infarction without significant coronary stenosis or atherosclerosis in patients with MPN suggests that vascular function is altered. Consequences of JAK2V617F mutation on vascular reactivity are unknown. We observe here increased responses to vasoconstrictors in arteries from Jak2V617F mice, resulting from disturbed endothelial nitric oxide pathway and increased endothelial oxidative stress. This response was reproduced in wild-type mice by circulating microvesicles isolated from patients carrying JAK2V617F and by erythrocyte-derived microvesicles from transgenic mice. Microvesicles of other cellular origins had no effect. This effect was observed ex vivo on isolated aortas, but also in vivo on femoral arteries. Proteomic analysis of microvesicles derived from JAK2V617F erythrocytes identified increased expression of myeloperoxidase as the likely mechanism accounting for microvesicles effect. Myeloperoxidase inhibition in microvesicles derived from JAK2V617F erythrocytes supressed their effect on oxidative stress. Antioxidants, such as simvastatin and N-acetyl-cysteine, improved arterial dysfunction in Jak2V617F mice. In conclusion, JAK2V617F MPN are characterized by exacerbated vasoconstrictor responses resulting from increased endothelial oxidative stress caused by circulating erythrocyte-derived microvesicles. Simvastatin appears as promising therapeutic strategy in this setting.

    J Clin Invest. 2020 Feb