Erythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm

Poisson, Johanne; Tanguy, Marion; Davy, Hortense; Camara, Fatoumata; Mdawar, Marie-Belle El; Kheloufi, Marouane; Dagher, Tracy; Devue, Cécile; Lasselin, Juliette; Plessier, Aurélie; Merchant, Salma; Blanc‐Brude, Olivier; Souyri, Michèle; Mougenot, Nathalie; Dingli, Florent; Loew, Damarys; Hatem, Stéphane; James, Chloé; Villeval, Jean‐Luc; Boulanger, Chantal M.; Rautou, Pierre‐Emmanuel

doi:10.1172/jci124566

Cited by 52 publications

(56 citation statements)

References 59 publications

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“…While most of the published studies have focused on mutant blood cells (eg, leukocytes, 33,63,64 red blood cells 65,66 ), two reports highlighted the pro‐adhesive phenotype of JAK2V617F mutant ECs using induced pluripotent stem cell lines from a MPN patient 62 or an endothelial‐specific JAK2V617F‐positive murine model 67 . However, no cardiovascular functional analysis was performed in these two studies.…”

Section: Discussionmentioning

confidence: 99%

Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm

Castiglione

Jiang

Mazzeo

et al. 2020

Journal of Thrombosis and Haemostasis

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Section: Discussionmentioning

confidence: 99%

Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm

Castiglione

Jiang

Mazzeo

et al. 2020

Journal of Thrombosis and Haemostasis

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“…RBCEVs impact on NO bioavailability depends on several factors including the abundance of particles entering the microcirculation and their proximity to the endothelium. In vitro and in vivo studies have shown that RBCEVs by enhancing ROS production disturb NO homeostasis leading to endothelial dysfunction [ 110 , 111 , 112 ]. RBCEVs from JAK2 V617F myeloproliferative neoplasms increase endothelial oxidative stress leading to NO pathway inhibition [ 111 ].…”

Section: Biological Roles Of Rbcevsmentioning

confidence: 99%

Extracellular Vesicles from Red Blood Cells and Their Evolving Roles in Health, Coagulopathy and Therapy

Thangaraju

Neerukonda

Katneni

et al. 2020

IJMS

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Red blood cells (RBCs) release extracellular vesicles (EVs) including both endosome-derived exosomes and plasma-membrane-derived microvesicles (MVs). RBC-derived EVs (RBCEVs) are secreted during erythropoiesis, physiological cellular aging, disease conditions, and in response to environmental stressors. RBCEVs are enriched in various bioactive molecules that facilitate cell to cell communication and can act as markers of disease. RBCEVs contribute towards physiological adaptive responses to hypoxia as well as pathophysiological progression of diabetes and genetic non-malignant hematologic disease. Moreover, a considerable number of studies focus on the role of EVs from stored RBCs and have evaluated post transfusion consequences associated with their exposure. Interestingly, RBCEVs are important contributors toward coagulopathy in hematological disorders, thus representing a unique evolving area of study that can provide insights into molecular mechanisms that contribute toward dysregulated hemostasis associated with several disease conditions. Relevant work to this point provides a foundation on which to build further studies focused on unraveling the potential roles of RBCEVs in health and disease. In this review, we provide an analysis and summary of RBCEVs biogenesis, composition, and their biological function with a special emphasis on RBCEV pathophysiological contribution to coagulopathy. Further, we consider potential therapeutic applications of RBCEVs.

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“…Dysfunction of the endothelium is associated with the appearance and progression of the most severe human diseases, including sepsis, diabetes, stroke, dementia, and cancer [5][6][7][8][9][10]. Although these diseases are characterized by specific alterations of the endothelium, some of which have yet to be fully elucidated, inflammation has been defined as a core pathological mechanism affecting vascular beds in all these pathologies [11,12].…”

Section: Introductionmentioning

confidence: 99%

System-wide molecular dynamics of endothelial dysfunction in Gram-negative sepsis

2020

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Background Inflammation affecting whole organism vascular networks plays a central role in the progression and establishment of several human diseases, including Gram-negative sepsis. Although the molecular mechanisms that control inflammation of specific vascular beds have been partially defined, knowledge lacks on the impact of these on the molecular dynamics of whole organism vascular beds. In this study, we have generated an in vivo model by coupling administration of lipopolysaccharide with stable isotope labeling in mammals to mimic vascular beds inflammation in Gram-negative sepsis and to evaluate its effects on the proteome molecular dynamics. Proteome molecular dynamics of individual vascular layers (glycocalyx (GC), endothelial cells (EC), and smooth muscle cells (SMC)) were then evaluated by coupling differential systemic decellularization in vivo with unbiased systems biology proteomics. Results Our data confirmed the presence of sepsis-induced disruption of the glycocalyx, and we show for the first time the downregulation of essential molecular maintenance processes in endothelial cells affecting this apical vascular coating. Similarly, a novel catabolic phenotype was identified in the newly synthesized EC proteomes that involved the impairment of protein synthesis, which affected multiple cellular mechanisms, including oxidative stress, the immune system, and exacerbated EC-specific protein turnover. In addition, several endogenous molecular protective mechanisms involving the synthesis of novel antithrombotic and anti-inflammatory proteins were also identified as active in EC. The molecular dynamics of smooth muscle cells in whole organism vascular beds revealed similar patterns of impairment as those identified in EC, although this was observed to a lesser extent. Furthermore, the dynamics of protein posttranslational modifications showed disease-specific phosphorylation sites in the EC proteomes. Conclusions Together, the novel findings reported here provide a broader picture of the molecular dynamics that take place in whole organism vascular beds in Gram-negative sepsis inflammation. Similarly, the obtained data can pave the way for future therapeutic strategies aimed at intervening in specific protein synthesis mechanisms of the vascular unit during acute inflammatory processes.

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Erythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm

Abstract: 8 Inserm UMS 28, Phénotypage du petit animal, Plateforme d'expérimentations coeur-muscle-vaisseaux (

Cited by 52 publications

References 59 publications

Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm

Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of myeloproliferative neoplasm

Extracellular Vesicles from Red Blood Cells and Their Evolving Roles in Health, Coagulopathy and Therapy

System-wide molecular dynamics of endothelial dysfunction in Gram-negative sepsis

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