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Article ; Online: Circulating endothelial cells in pathophysiology.

Brett, Victor Emmanuel / Dignat George, Francoise / James, Chloe

2024 Volume 31, Issue 3, Page(s) 148–154

Abstract: Purpose of review: The purpose of this review is to synthesize recent insights into the roles and importance of circulating endothelial cells (CECs) as indicators of the severity, progression, and prognosis of vascular-related diseases.: Recent ... ...

Abstract	Purpose of review: The purpose of this review is to synthesize recent insights into the roles and importance of circulating endothelial cells (CECs) as indicators of the severity, progression, and prognosis of vascular-related diseases. Recent findings: Recent studies have identified elevated counts of CECs in pathological conditions, notably inflammatory or cardiovascular diseases such as acute myocardial infarction and heart failure, underscoring their potential as sensitive indicators of disease. Furthermore, the rise in CEC levels in cancer patients, particularly with disease advancement, points to their role in cancer-associated angiogenesis and response to treatment. Summary: This review underscores the evolving significance of CECs as markers for evaluating the gravity and advancement of diseases with vascular injury, including cardiovascular diseases, cancer, inflammatory conditions, and thromboembolic events. These last years, efforts made to standardize flow cytometry detection of CEC and the development of highly sensitive techniques to isolate, quantify or phenotype rare cells open promising avenues for clinical application. This may yield extensive knowledge regarding the mechanisms by which endothelial cells contribute to a variety of vascular-related disorders and their clinical value as emerging biomarkers.
MeSH term(s)	Humans ; Endothelial Cells/pathology ; Biomarkers ; Myocardial Infarction ; Vascular Diseases/pathology ; Neoplasms/pathology ; Flow Cytometry
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000814
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Article: Is Endothelial Activation a Critical Event in Thrombotic Thrombocytopenic Purpura?

Cauchois, Raphael / Muller, Romain / Lagarde, Marie / Dignat-George, Françoise / Tellier, Edwige / Kaplanski, Gilles

Journal of clinical medicine

2023 Volume 12, Issue 3

Abstract: Thrombotic thrombocytopenic purpura (TTP) is a severe thrombotic microangiopathy. The current pathophysiologic paradigm suggests that the ADAMTS13 deficiency leads to Ultra Large-Von Willebrand Factor multimers accumulation with generation of ... ...

Abstract	Thrombotic thrombocytopenic purpura (TTP) is a severe thrombotic microangiopathy. The current pathophysiologic paradigm suggests that the ADAMTS13 deficiency leads to Ultra Large-Von Willebrand Factor multimers accumulation with generation of disseminated microthrombi. Nevertheless, the role of endothelial cells in this pathology remains an issue. In this review, we discuss the various clinical, in vitro and in vivo experimental data that support the important role of the endothelium in this pathology, suggesting that ADAMTS13 deficiency may be a necessary but not sufficient condition to induce TTP. The "second hit" model suggests that in TTP, in addition to ADAMTS13 deficiency, endogenous or exogenous factors induce endothelial activation affecting mainly microvascular cells. This leads to Weibel-Palade bodies degranulation, resulting in UL-VWF accumulation in microcirculation. This endothelial activation seems to be worsened by various amplification loops, such as the complement system, nucleosomes and free heme.
Language	English
Publishing date	2023-01-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12030758
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Article ; Online: Biomarqueurs vésiculaires - Opportunités et défis dans les maladies cardiovasculaires et les cancers.

Bonifay, Amandine / Ghayad, Sandra / Lacroix, Romaric / Dignat-George, Françoise

Medecine sciences : M/S

2021 Volume 37, Issue 12, Page(s) 1158–1165

Abstract: Cardiovascular diseases and cancer are the leading causes of mortality and morbidity in the world. The search for pertinent biomarkers for risk stratification and treatment monitoring is a challenge. Rapid advances in the identification of the molecular ... ...

Title translation	Extracellular vesicles-associated biomarkers: Opportunities and challenges in cardiovascular diseases and cancer.
Abstract	Cardiovascular diseases and cancer are the leading causes of mortality and morbidity in the world. The search for pertinent biomarkers for risk stratification and treatment monitoring is a challenge. Rapid advances in the identification of the molecular and functional content of extracellular vesicles (EV) and ongoing progress in developing highly sensitive methodologies, identify EV as promising biomarkers easily accessible in liquid biopsies. Thanks to robust and sensitive methodologies, the measurability of biological targets on EV allows to define vesicular biomarkers pertinent for disease management. Adaptation of the pre-analytical and analytical steps to each EV-associated biomarker, technological improvement and standardization efforts driven by scientific societies are essential prerequisites to accelerate the transfer of these EV-associated biomarkers to the clinics and to support the development of personalized medicine.
MeSH term(s)	Biomarkers ; Cardiovascular Diseases/diagnosis ; Extracellular Vesicles ; Humans ; Neoplasms/diagnosis ; Neoplasms/therapy
Chemical Substances	Biomarkers
Language	French
Publishing date	2021-12-20
Publishing country	France
Document type	Journal Article
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2021208
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Article ; Online: Mortality, cardiac and cerebral damages reduction by IL-1 inhibition in a murine model of TTP.

Muller, Romain / Cauchois, Raphael / Lagarde, Marie / Roffino, Sandrine / Genovesio, Cecile / Fernandez, Samantha / Hache, Guillaume / Guillet, Benjamin / Kara, Yeter / Marlinge, Marion / Lenting, Peter J / Poullin, Pascale / Dignat-George, Françoise / Tellier, Edwige / Kaplanski, Gilles

Blood

2024

Abstract: Thrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in Von Willebrand factor cleavage resulting in capillary microthrombi formation and ischemic organ damage. Interleukin-1 (IL-1), has been shown to ... ...

Abstract	Thrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in Von Willebrand factor cleavage resulting in capillary microthrombi formation and ischemic organ damage. Interleukin-1 (IL-1), has been shown to drive sterile inflammation following ischemia and could play an essential contribution to post-ischemic organ damage in TTP. Our objectives were to evaluate IL-1 involvement during TTP and to test the efficacy of the recombinant IL-1 receptor antagonist, anakinra, in a murine TTP model. We retrospectively measured plasmatic IL-1 concentrations in TTP patients and controls. TTP patients exhibited elevated plasma IL-1α and β concentrations, which correlated with disease course and survival. In a TTP mouse model, we administered anakinra (IL-1 inhibitor) or placebo for 5 days and evaluated the efficacy of this treatment. Anakinra significantly reduced mortality of mice (P<0.001). Anakinra significantly decreased TTP-induced cardiac damages as assessed by blood troponin concentrations, evaluation of left ventricular function by echocardiography, [18F]FDG PET of myocardial glucose metabolism, and cardiac histology. Anakinra also significantly reduced brain TTP-induced damages, evaluated through blood PS100b concentrations, nuclear imaging and histology. We finally showed that IL-1α and β trigger endothelial degranulation in vitro, leading to the release of Von Willebrand factor. In conclusion, Anakinra significantly reduced TTP mortality in a pre-clinical model of the disease by inhibiting both endothelial degranulation and post-ischemic inflammation, supporting further evaluations in humans.
Language	English
Publishing date	2024-04-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023021974
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Article: Rheopheresis Performed in Hemodialysis Patients Targets Endothelium and Has an Acute Anti-Inflammatory Effect.

Solignac, Justine / Lacroix, Romaric / Arnaud, Laurent / Abdili, Evelyne / Bouchouareb, Dammar / Burtey, Stéphane / Brunet, Philippe / Dignat-George, Françoise / Robert, Thomas

Journal of clinical medicine

2022 Volume 12, Issue 1

Abstract: Background: Rheopheresis is a double-filtration plasmapheresis that removes a defined spectrum of high-molecular-weight proteins to lower plasma viscosity and improves microcirculation disorders. This technique can be performed in hemodialysis (HD) ... ...

Abstract	Background: Rheopheresis is a double-filtration plasmapheresis that removes a defined spectrum of high-molecular-weight proteins to lower plasma viscosity and improves microcirculation disorders. This technique can be performed in hemodialysis (HD) patients with severe microischemia. Interestingly, some studies showed that rheopheresis sessions improve endothelial function. Methods: Our study evaluated the inflammatory and endothelial biomarker evolution in 23 HD patients treated or not with rheopheresis. A p value ≤ 0.001 was considered statistically significant. Results: Thirteen HD patients treated by rheopheresis either for a severe peripheral arterial disease (N = 8) or calciphylaxis (N = 5) were analyzed. Ten control HD patients were also included in order to avoid any misinterpretation of the rheopheresis effects in regard to the HD circuit. In the HD group without rheopheresis, the circulating endothelial adhesion molecules, cytokines, angiogenic factor concentrations, and circulating levels were not modified. In the HD group with rheopheresis, the circulating endothelial adhesion molecules (sVCAM-1, sP-selectin, and sE-selectin) experienced a significant reduction, except sICAM-1. Among the pro-inflammatory cytokines, TNF-α was significantly reduced by 32.6% [(−42.2)−(−22.5)] (p < 0.0001), while the anti-inflammatory cytokine IL-10 increased by 674% (306−1299) (p < 0.0001). Among the angiogenic factors, only sEndoglin experienced a significant reduction. The CEC level trended to increase from 13 (3−33) cells/mL to 43 (8−140) cells/mL (p = 0.002). We did not observe any difference on the pre-session values of the molecules of interest between the first rheopheresis session and the last rheopheresis session. Conclusion: Rheopheresis immediately modified the inflammation balance and the endothelial injury biomarkers. Further studies are needed to understand the mechanisms underlying these biological observations.
Language	English
Publishing date	2022-12-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12010105
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Article ; Online: Commentary about mesenchymal stem cells and scarred vocal folds.

Mattei, Alexia / Magalon, Jérémy / Velier, Mélanie / Dignat-George, Françoise / Giovanni, Antoine / Sabatier, Florence

Stem cell research & therapy

2020 Volume 11, Issue 1, Page(s) 173

Abstract: A commentary to "Hertegård, S., Nagubothu, S.R., Malmström, E. et al. Treatment of vocal fold scarring with autologous bone marrow-derived human mesenchymal stromal cells - first phase I/II human clinical study. Stem Cell Res Ther 11, 128 (2020)" ... ...

Abstract	A commentary to "Hertegård, S., Nagubothu, S.R., Malmström, E. et al. Treatment of vocal fold scarring with autologous bone marrow-derived human mesenchymal stromal cells - first phase I/II human clinical study. Stem Cell Res Ther 11, 128 (2020)" concerning the surgical intervention including a scar resection, the use of the Voice Handicap Index, the surgical and regulatory points of view regarding the inclusion of patients with laryngeal carcinomas history, and the side effects of bone marrow harvesting.
MeSH term(s)	Bone Marrow ; Cicatrix ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Vocal Cords
Language	English
Publishing date	2020-05-07
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-020-01693-9
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Article ; Online: Resveratrol Reverses Endothelial Colony-Forming Cell Dysfunction in Adulthood in a Rat Model of Intrauterine Growth Restriction.

Guillot, Estelle / Lemay, Anna / Allouche, Manon / Vitorino Silva, Sara / Coppola, Hanna / Sabatier, Florence / Dignat-George, Françoise / Sarre, Alexandre / Peyter, Anne-Christine / Simoncini, Stéphanie / Yzydorczyk, Catherine

International journal of molecular sciences

2023 Volume 24, Issue 11

Abstract: Individuals born after intrauterine growth restriction (IUGR) are at risk of developing cardiovascular diseases (CVDs). Endothelial dysfunction plays a role in the pathogenesis of CVDs; and endothelial colony-forming cells (ECFCs) have been identified as ...

Abstract	Individuals born after intrauterine growth restriction (IUGR) are at risk of developing cardiovascular diseases (CVDs). Endothelial dysfunction plays a role in the pathogenesis of CVDs; and endothelial colony-forming cells (ECFCs) have been identified as key factors in endothelial repair. In a rat model of IUGR induced by a maternal low-protein diet, we observed an altered functionality of ECFCs in 6-month-old males, which was associated with arterial hypertension related to oxidative stress and stress-induced premature senescence (SIPS). Resveratrol (R), a polyphenol compound, was found to improve cardiovascular function. In this study, we investigated whether resveratrol could reverse ECFC dysfunctions in the IUGR group. ECFCs were isolated from IUGR and control (CTRL) males and were treated with R (1 μM) or dimethylsulfoxide (DMSO) for 48 h. In the IUGR-ECFCs, R increased proliferation (5'-bromo-2'-deoxyuridine (BrdU) incorporation,
MeSH term(s)	Humans ; Male ; Female ; Rats ; Animals ; Fetal Growth Retardation/metabolism ; Resveratrol/pharmacology ; Resveratrol/metabolism ; Fluorescent Dyes/metabolism ; Endothelial Cells/metabolism ; Cardiovascular Diseases/metabolism ; Cell Proliferation ; Cells, Cultured
Chemical Substances	Resveratrol (Q369O8926L) ; Fluorescent Dyes
Language	English
Publishing date	2023-06-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24119747
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Article: Microvesicles Are Associated with Early Veno Venous ECMO Circuit Change during Severe ARDS: A Prospective Observational Pilot Study.

Guervilly, Christophe / Bousquet, Giovanni / Arnaud, Laurent / Gragueb-Chatti, Ines / Daviet, Florence / Adda, Mélanie / Forel, Jean-Marie / Dignat-George, Françoise / Papazian, Laurent / Roch, Antoine / Lacroix, Romaric / Hraiech, Sami

Journal of clinical medicine

2023 Volume 12, Issue 23

Abstract: Background: Veno venous Extra Corporeal Membrane Oxygenation (vvECMO) is associated with frequent hematological ECMO-related complications needing ECMO circuit change. Microvesicles (MVs) interplay during the thrombosis-fibrinolysis process. The main ... ...

Abstract	Background: Veno venous Extra Corporeal Membrane Oxygenation (vvECMO) is associated with frequent hematological ECMO-related complications needing ECMO circuit change. Microvesicles (MVs) interplay during the thrombosis-fibrinolysis process. The main objective of the study was to identify subpopulations of MVs associated with indications of early vvECMO circuit change. Methods: This is a prospective observational monocenter cohort study. Blood gas was sampled on the ECMO circuit after the membrane oxygenator to measure the PO Results: Nineteen patients were investigated. Seven patients (37%) needed an ECMO circuit change for hemolysis (n = 4), a pump thrombosis with fibrinolysis (n = 1), persistent thrombocytopenia with bleeding (n = 1) and a decrease of O Conclusions: Our pilot study supports the potential interest of subpopulations of microvesicles early associated with hematological ECMO-related complications. Our results warrant further studies.
Language	English
Publishing date	2023-11-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12237281
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Article ; Online: Immune-mediated thrombotic thrombocytopenic purpura plasma induces calcium- and IgG-dependent endothelial activation: correlations with disease severity.

Tellier, Edwige / Widemann, Agnès / Cauchois, Raphaël / Faccini, Julien / Lagarde, Marie / Brun, Marion / Robert, Philippe / Robert, Stéphane / Bachelier, Richard / Poullin, Pascale / Roose, Elien / Vanhoorelbeke, Karen / Coppo, Paul / Dignat-George, Françoise / Kaplanski, Gilles

Haematologica

2023 Volume 108, Issue 4, Page(s) 1127–1140

Abstract: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by a severe ADAMTS13 deficiency due to the presence of anti-ADAMTS13 auto-antibodies, with subsequent accumulation of circulating ultra-large von Willebrand factor (VWF) ... ...

Abstract	Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by a severe ADAMTS13 deficiency due to the presence of anti-ADAMTS13 auto-antibodies, with subsequent accumulation of circulating ultra-large von Willebrand factor (VWF) multimers. The role of endothelial cell activation as a trigger of the disease has been suggested in animal models but remains to be demonstrated in humans. We prospectively obtained plasma from the first plasma exchange of 25 patients during iTTP acute phase. iTTP but not control plasma, induced a rapid VWF release and P-selectin exposure on the surface of dermal human micro-vascular endothelial cell (HMVEC-d), associated with angiopoietin-2 and endothelin-1 secretion, consistent with Weibel-Palade bodies exocytosis. Calcium (Ca2+) blockade significantly decreased VWF release, whereas iTTP plasma induced a rapid and sustained Ca2+ flux in HMVEC-d which correlated in retrospect, with disease severity and survival in 62 iTTP patients. F(ab)'2 fragments purified from the immunoglobulin G fraction of iTTP plasma mainly induced endothelial cell activation with additional minor roles for circulating free heme and nucleosomes, but not for complement. Furthermore, two anti-ADAMTS13 monoclonal antibodies purified from iTTP patients' B cells, but not serum from hereditary TTP, induced endothelial Ca2+ flux associated with Weibel-Palade bodies exocytosis in vitro, whereas inhibition of endothelial ADAMTS13 expression using small intering RNA, significantly decreased the stimulating effects of iTTP immunoglobulin G. In conclusion, Ca2+-mediated endothelial cell activation constitutes a "second hit" of iTTP, is correlated with the severity of the disease and may constitute a possible therapeutic target.
MeSH term(s)	Animals ; Humans ; Purpura, Thrombotic Thrombocytopenic ; Calcium ; von Willebrand Factor/metabolism ; Immunoglobulin G ; ADAMTS13 Protein ; Patient Acuity
Chemical Substances	Calcium (SY7Q814VUP) ; von Willebrand Factor ; Immunoglobulin G ; ADAMTS13 Protein (EC 3.4.24.87)
Language	English
Publishing date	2023-04-01
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.280651
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Article ; Online: Microparticles: new protagonists in pericellular and intravascular proteolysis.

Lacroix, Romaric / Dignat-George, Francoise

Seminars in thrombosis and hemostasis

2013 Volume 39, Issue 1, Page(s) 33–39

Abstract: Microparticles (MPs) are small vesicles resulting from the shedding of cellular membrane during activation or apoptosis processes. Beyond their well-described procoagulant property, accumulating data show that specific endothelial cell-, leukocyte-, ... ...

Abstract	Microparticles (MPs) are small vesicles resulting from the shedding of cellular membrane during activation or apoptosis processes. Beyond their well-described procoagulant property, accumulating data show that specific endothelial cell-, leukocyte-, tumor-derived MPs bind plasminogen and vectorize plasminogen activators, leading to an efficient plasmin generation and matrix metalloproteinases activation. This review focuses on the molecular equipment of MPs subpopulations that identify MPs as efficient support for plasmin generation and the potential consequences of this new function. By the combined facts that MPs may disseminate, concentrate active proteolytic molecules and represent a protective environment against soluble inhibitors, MPs behave as an efficient catalytic surface involved in vascular and matrix proteolysis-related biological processes. The existence of this proteolytic MPs in the circulation or in body fluids raises the question about the physiological relevance of this activity. Consequences are suggested in many biological processes such as fibrinolysis, cell survival, matrix remodeling, angiogenesis, and tumor metastasis. However, further studies will be necessary to determine the extent in which in vivo MPs contribute to these pathophysiological mechanisms and how this circulating property of MPs may represent a new biomarker in specific clinical situations.
MeSH term(s)	Cell-Derived Microparticles/metabolism ; Endothelial Cells/metabolism ; Fibrinolysin/metabolism ; Humans ; Leukocytes/metabolism ; Matrix Metalloproteinases/metabolism ; Models, Biological ; Neoplasms/metabolism ; Neoplasms/pathology ; Plasminogen/metabolism ; Proteolysis
Chemical Substances	Plasminogen (9001-91-6) ; Fibrinolysin (EC 3.4.21.7) ; Matrix Metalloproteinases (EC 3.4.24.-)
Language	English
Publishing date	2013-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0032-1333310
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