Claire Peghaire

University of Bordeaux-INSERM U1034 · College of Health Sciences-Biology of Cardiovascular Diseases

Cerebral small vessel disease (SVD) is a leading cause of strokes and a significant contributor to dementia, yet the precise mechanisms underlying its pathogenesis remain elusive. In a recent whole-exome association study involving population cohorts with SVD, we identified a variant on TRIM47 locus. The ubiquitin ligase TRIM47 is highly expressed...

The haemostatic system involves an array of circulating coagulation factors, which work in concert with platelets and the vascular endothelium to promote clotting in a space and time-defined manner. Despite the equal systemic exposure to circulating factors, bleeding and thrombotic diseases tend to prefer specific sites, suggesting an important rol...

Current dogma dictates that, during adulthood, endothelial cells (ECs) are locked in an immutable stable homeostatic state. By contrast, herein we show that maintenance of EC fate and function are linked and active processes, which depend on the constitutive cooperativity of only two ETS transcription factors (TFs), ERG and Fli1. Although deletion...

The Wnt/frizzled signaling pathway is one of the major regulators of endothelial biology, controlling key cellular activities. Many secreted Wnt ligands have been identified and can initiate diverse signaling via binding to a complex set of Frizzled (Fzd) transmembrane receptors and coreceptors. Roughly, Wnt signaling is subdivided into two pathway...

A striking feature of severe COVID-19 is thrombosis in large as well as small vessels of multiple organs. This has led to the assumption that SARS-CoV-2 virus directly infects and damages the vascular endothelium. However, endothelial expression of ACE2, the cellular receptor for SARS-CoV-2, has not been convincingly demonstrated. Interrogating hum...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Retinopathies remain major causes of visual impairment in diabetic patients and premature infants. Introduction of anti‐angiogenic drugs targeting vascular endothelial growth factor (VEGF) has transformed therapy for these proliferative retinopathies. However, limitations associated with anti‐VEGF medications require to unravel new pathways of vess...

Endothelial cells actively maintain an anti-thrombotic environment; loss of this protective function may lead to thrombosis and systemic coagulopathy. The transcription factor ERG is essential to maintain endothelial homeostasis. Here, we show that inducible endothelial ERG deletion (ErgiEC-KO) in mice is associated with spontaneous thrombosis, hem...

During wound healing, the distribution, availability, and signaling of growth factors (GFs) are orchestrated by their binding to extracellular matrix components in the wound microenvironment. Extracellular matrix proteins have been shown to modulate angiogenesis and promote wound healing through GF binding. The hemostatic protein von Willebrand fac...

Rationale: The ETS (E-26 transformation-specific) transcription factor ERG (ETS-related gene) is essential for endothelial homeostasis, driving expression of lineage genes and repressing proinflammatory genes. Loss of ERG expression is associated with diseases including atherosclerosis. ERG's homeostatic function is lineage-specific, because aberr...

Background The vessel wall, and particularly blood endothelial cells (BEC) are intensively studied to better understand hemostasis and target thrombosis. To understand the specific role of BEC, it is important to have mouse models that allow specific and homogeneous expression of genes of interest in all BEC beds without concomitant expression in b...

Thrombosis is the main cause of morbidity and mortality in patients with JAK2V617F myeloproliferative neoplasms. Recent studies have reported the presence of JAK2V617F in endothelial cells of some patients with MPN. We investigated the role of endothelial cells that express JAK2V617F in thrombus formation using an in vitro model of human endothelia...

The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis sho...

Notch and Angiopoietin-1 (Ang1)/Tie2 pathways are crucial for vascular maturation and stability. Here we identify the transcription factor ERG as a key regulator of endothelial Notch signalling. We show that ERG controls the balance between Notch ligands by driving Delta-like ligand 4 (Dll4) while repressing Jagged1 (Jag1) expression. In vivo, this...

Objective: Vessel formation requires precise orchestration of a series of morphometric and molecular events controlled by a multitude of angiogenic factors and morphogens. Wnt/frizzled signaling is required for proper vascular formation. In this study, we investigated the role of the Fzd7 (frizzled-7) receptor in retinal vascular development and i...

Blinding diseases including retinopathy of prematurity and proliferative diabetic retinopathy are the consequence of pathological angiogenesis in the retina. A better understanding of the mechanisms involved in this abnormal proliferation of neovessels appears to be essential to develop drugs against new molecular targets. Recently, we have evidenc...

Angiogenesis involves the coordinated growth and migration of endothelial cells (EC) toward a proangiogenic signal. The Wnt Planar Cell Polarity (PCP) pathway, through the recruitment of Dishevelled (Dvl) and Dvl associated activator of morphogenesis (Daam1), has been proposed to regulate cell actin cytoskeleton and microtubule (MT) reorganization...

Growing evidence has shown that Wnt/Fzd proteins are expressed in vascular cells and are directly involved in blood vessel development by regulating endothelial cell (EC) properties. In this study, we analyzed the effects of frizzled7 deficiency in EC on vessel formation in the postnatal mouse retina. We generated fzd7F/F mice and crossed them with...

Physiological angiogenesis is a key process in embryonic development but also in adult. Abnormal formation of blood vessels is the cause of many diseases. A better understanding of the mechanisms of angiogenesis is an essential prerequisite for the development of new therapeutic strategies aimed to inhibit or stimulate angiogenesis to better addres...

Development and stabilization of a vascular plexus requires the coordination of multiple signalling processes. Wnt planar cell polarity (PCP) signalling is critical in vertebrates for diverse morphogenesis events, which coordinate cell orientation within a tissue-specific plane. However, its functional role in vascular morphogenesis is not well und...

Aims: Vascular permeability is essential for the health of normal tissues and is an important characteristic of many disease states. The role of the Wnt/frizzled pathway in vascular biology has recently been reported. The objectives of this study are to analyse the role of Frizzled7 (Fzd7) receptor in the control of vascular integrity. Methods an...