Marie-Lise Bats - Academia.edu (original) (raw)

Papers by Marie-Lise Bats

Research paper thumbnail of Impact of albumin assays in the diagnosis of malnutrition in hemodialysis patients: a cohort study

Journal of Renal Nutrition

Research paper thumbnail of PHACTR-1 (Phosphatase and Actin Regulator 1) Deficiency in Either Endothelial or Smooth Muscle Cells Does Not Predispose Mice to Nonatherosclerotic Arteriopathies in 3 Transgenic Mice

Arteriosclerosis, Thrombosis, and Vascular Biology

Background: Genome-wide association studies have revealed robust associations of common genetic p... more Background: Genome-wide association studies have revealed robust associations of common genetic polymorphisms in an intron of the PHACTR-1 (phosphatase and actin regulator 1) gene (chr6p24), with cervical artery dissection, spontaneous coronary artery dissection, and fibromuscular dysplasia. The aim was to assess its role in the pathogenesis of cervical artery dissection or fibromuscular dysplasia. Methods: Using various tissue-specific Cre-driver mouse lines, Phactr1 was deleted either in endothelial cells using 2 tissue-specific Cre-driver (PDGFB [platelet-derived growth factor B]-Cre ERT2 mice and Tie2 [tyrosine kinase with immunoglobulin and EGF homology domains]-Cre) and smooth muscle cells (smooth muscle actin-Cre ERT2 ) with a third tissue-specific Cre-driver. Results: To test the efficacy of the Phactr1 deletion after cre-induction, we confirmed first, a decrease in Phactr1 transcription and Phactr1 expression in endothelial cell and smooth muscle cell isolated from Phactr1 ...

Research paper thumbnail of Increased Capillary Permeability in Heart Induces Diastolic Dysfunction Independently of Inflammation, Fibrosis, or Cardiomyocyte Dysfunction

Arteriosclerosis, Thrombosis, and Vascular Biology

Background: While endothelial dysfunction is suggested to contribute to heart failure with preser... more Background: While endothelial dysfunction is suggested to contribute to heart failure with preserved ejection fraction pathophysiology, understanding the importance of the endothelium alone, in the pathogenesis of diastolic abnormalities has not yet been fully elucidated. Here, we investigated the consequences of specific endothelial dysfunction on cardiac function, independently of any comorbidity or risk factor (diabetes or obesity) and their potential effect on cardiomyocyte. Methods: The ubiquitine ligase Pdzrn3 , expressed in endothelial cells (ECs), was shown to destabilize tight junction. A genetic mouse model in which Pdzrn3 is overexpressed in EC (iEC-Pdzrn3) in adults was developed. Results: EC-specific Pdzrn3 expression increased cardiac leakage of IgG and fibrinogen blood-born molecules. The induced edema demonstrated features of diastolic dysfunction, with increased end-diastolic pressure, alteration of dP/dt min, increased natriuretic peptides, in addition to limited e...

Research paper thumbnail of ROR2 in post-natal vessel formation

Archives of Cardiovascular Diseases Supplements, 2018

Research paper thumbnail of Plasma creatinine below limit of quantification in a patient with acute kidney injury

Clinica Chimica Acta, 2022

Acute kidney injury (AKI) is an infrequent complication of inflammatory bowel disease and can be ... more Acute kidney injury (AKI) is an infrequent complication of inflammatory bowel disease and can be exceptionally linked to interstitial nephritis secondary to anti-inflammatory drugs, such as Pentasa® (5-ASA). Case presentation We present an case of an 80-year-old man who presented chronic diarrheas treated by Pentasa®. He developed AKI, evidenced by high plasma creatinine dosed in his local laboratory. At the hospital admission, plasma creatinine was exceptionally undetectable by the enzymatic method while Jaffe's method successfully determined it. Creatinine measurement by the enzymatic method was gradually restored during hospital stay, concomitant with the discontinuation of 5-ASA administration, suggesting that this drug could interfere with creatinine enzymatic assay. Creatinine enzymatic assays combine serial reactions. The last one called Trinder reaction, catalyzed by a peroxidase, uses H2O2 to convert uncolored dye in a colored compound, proportionally to creatinine concentration. We showed that AKI related-plasma accumulation of 5-ASA, could participate in the negative interference observed on creatinine measurement, by scavenging H2O2. Interestingly, all Trinder reaction-based measurements (uric acid, lipase, lactate, triglycerides and cholesterol) were affected. Negative interference of 5-ASA was confirmed by interferogram experiments on all Trinder reaction-dependent assays. All Trinder-dependent parameters should be interpreted with the patient's treatment knowledge, in particular salicylate derivatives.

Research paper thumbnail of No direct involvement of Phactr-1 in non-atherosclerotic arteriopathies: results from 3 different Phactr-1 transgenic knockout mice

European Heart Journal, 2021

Introduction Genome-wide association studies have revealed robust associations of common genetic ... more Introduction Genome-wide association studies have revealed robust associations of common genetic polymorphisms in the Phactr1 locus (6p24) (encoding Phosphatase and Actin Regulator 1) with cervico-cerebral artery dissection (CCeAD), spontaneous coronary artery dissection (SCAD) and fibromuscular dysplasia (FMD). These common elements of genetic predisposition provide a proof of concept for important shared mechanisms at the molecular level between CCeAD, SCAD and FMD vascular diseases. Objective Deciphering genetic, molecular and physiological importance of PHACTR1. Method Using various tissue-specific Cre-driver mouse lines, Phactr1 was deleted either in endothelial cells (EC) using 2 tissue-specific Cre-driver (one of them was embryonic) and Smooth Muscle Cells (SMC) with a third tissue-specific Cre-driver to assess its role in the pathogenesis of CCeAD, SCAD or FMD. Results To test the efficacy of the Phactr1 deletion after cre-induction, we confirmed firstly, a decrease in Phact...

Research paper thumbnail of Wnt/frizzled Signaling in Endothelium: A Major Player in Blood-Retinal- and Blood-Brain-Barrier Integrity

Cold Spring Harbor Perspectives in Medicine, 2022

The Wnt/frizzled signaling pathway is one of the major regulators of endothelial biology, control... more 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 pathways: the canonical Wnt/β-catenin signaling pathway whose main downstream effector is the transcriptional coactivator β-catenin, and the noncanonical Wnt signaling pathway, which is subdivided into the Wnt/Ca2+ pathway and the planar cell polarity pathway. Here, we will focus on its cross talk with other angiogenic pathways and on its role in blood-retinal- and blood-brain-barrier formation and its maintenance in a differentiated state. We will unravel how retinal vascular pathologies and neurovascular degenerative diseases result from disruption of the Wnt pathway related to vascular instability, and highlight current research into therapeutic options.

Research paper thumbnail of Article original Acidose lactique et interférence analytique lors du dosage de l'éthylène glycol selon une méthode colorimétrique : à propos d'un cas Analytical interference between lactates and ethylene glycol: a case report

Research paper thumbnail of Abrogating Frizzled7 in endothelial cell protects against the development of pathological angiogenesis during proliferative retinopathy

Archives of Cardiovascular Diseases Supplements

Research paper thumbnail of Pigments test strips: A rapid companion test to exclude sub-arachnoid haemorrhage

Research paper thumbnail of Mast Cells Are the Trigger of Small Vessel Disease and Diastolic Dysfunction in Diabetic Obese Mice

Arteriosclerosis, Thrombosis, and Vascular Biology

Objective: Heart failure with preserved ejection fraction is a major health care issue which has ... more Objective: Heart failure with preserved ejection fraction is a major health care issue which has been difficult to manage to date, due to its complex and not well understood pathophysiology. Specifically, if a wealth of literature focuses on heart failure with preserved ejection fraction cardiac component, very little information can be found on its vascular component. Our goal is to unravel the critical role of cardiac small vessel disease in the pathophysiology of diastolic dysfunction. Approach and Results: To do so, we used leptin receptor deficient (Lepr db/db ) female mice, a recognized model of diastolic dysfunction. In these mice, the increased end-diastolic pressure signing diastolic dysfunction is associated with vascular leakage, endothelial cell activation, and leucocyte infiltration. Strikingly, a RNA sequencing analysis of the cardiac vascular fraction of both Lepr db/db and control mice confirmed endothelial dysfunction and systemic inflammation, but above all, reveal...

Research paper thumbnail of Covichem: A biochemical severity risk score of COVID-19 upon hospital admission

PLOS ONE

Clinical and laboratory predictors of COVID-19 severity are now well described and combined to pr... more Clinical and laboratory predictors of COVID-19 severity are now well described and combined to propose mortality or severity scores. However, they all necessitate saturable equipment such as scanners, or procedures difficult to implement such as blood gas measures. To provide an easy and fast COVID-19 severity risk score upon hospital admission, and keeping in mind the above limits, we sought for a scoring system needing limited invasive data such as a simple blood test and co-morbidity assessment by anamnesis. A retrospective study of 303 patients (203 from Bordeaux University hospital and an external independent cohort of 100 patients from Paris Pitié-Salpêtrière hospital) collected clinical and biochemical parameters at admission. Using stepwise model selection by Akaike Information Criterion (AIC), we built the severity score Covichem. Among 26 tested variables, 7: obesity, cardiovascular conditions, plasma sodium, albumin, ferritin, LDH and CK were the independent predictors of...

Research paper thumbnail of Mast cells participate in the development of diastolic dysfunction in diabetic obese mice

RationalHeart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic issue. ... more RationalHeart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic issue. However, to date, its pathophysiology remains poorly understood.ObjectiveOur goal was to investigate the role of microvessel disease in the pathophysiology of diastolic dysfunction.FindingsTo do so, we used Leptin receptor deficient (Leprdb/db) female mice as a model of diastolic dysfunction. In these mice, the increased end diastolic pressure (EDP) signing diastolic dysfunction is associated with vascular leakage, endothelial cell activation and leucocyte infiltration. Strikingly, a RNA sequencing analysis of the cardiac vascular fraction of both Leprdb/db and control female mice confirmed endothelial dysfunction and systemic inflammation but also revealed a strong increase in several mast cell markers (notably FceR1a, Tryptase and Chymase). We then histologically confirmed an accumulation of activated mast cells in the heart of Leprdb/db mice. Importantly, mast cell degranulation inhib...

Research paper thumbnail of Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019

Clinical Kidney Journal

Background Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, se... more Background Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported. Methods Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated. Results Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12–23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35...

Research paper thumbnail of Characterisation of Acute Kidney Injury in Critically Ill Patients with Severe Coronavirus Disease-2019 (COVID-19)

Background: COVID19-associated acute kidney injury frequency, severity and characterisation in cr... more Background: COVID19-associated acute kidney injury frequency, severity and characterisation in critically ill patients has not been reported. Methods: Single-center cohort performed from March 3, 2020, to April 14, 2020 in 4 intensive care units in Bordeaux University Hospital, France. All patients with COVID19 and pulmonary severity criteria were included. AKI was defined using KDIGO criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterisation (transient vs. persistent acute kidney injury; proteinuria, hematuria and glycosuria), and short-term outcomes was evaluated. Results: 71 patients were included, with basal serum creatinine of 69 +/- 21 micromol/L. At admission, AKI was present in 8/71 (11%) patients. Median follow-up was 17 [12-23] days. AKI developed in a total of 57/71 (80%) patients with 35% Stage 1, 35% Stage 2, and 30% Stage 3 acute kidney injury; 10/57 (18%) required renal replacement therapy. Transi...

Research paper thumbnail of Therapies targeting Frizzled‐7/β‐catenin pathway prevent the development of pathological angiogenesis in an ischemic retinopathy model

Research paper thumbnail of Comparison of endothelial promoter efficiency and specificity in mice reveals a subset of Pdgfb‐positive hematopoietic cells

Journal of Thrombosis and Haemostasis

Research paper thumbnail of A combined approach for the early recognition of acute kidney injury after adult cardiac surgery

Anaesthesia Critical Care & Pain Medicine

Research paper thumbnail of Targeting the sphingosine 1-phosphate axis exerts potent antitumor activity in BRAFi-resistant melanomas

Molecular Cancer Therapeutics

BRAF inhibitors (BRAFi) are used to treat patients with melanoma harboring the V600E mutation. Ho... more BRAF inhibitors (BRAFi) are used to treat patients with melanoma harboring the V600E mutation. However, resistance to BRAFi is inevitable. Here, we identified sphingosine 1-phosphate (S1P) receptors as regulators of BRAF V600Emutant melanoma cell-autonomous resistance to BRAFi. Moreover, our results reveal a distinct sphingolipid profile, that is, a tendency for increased very long-chain ceramide species, in the plasma of patients with melanoma who achieve a response to BRAFi therapy as compared with patients with progressive disease. Treatment with BRAFi resulted in a strong decrease in S1PR1/3 expression in sensitive but not in resistant cells. Genetic and pharmacologic interventions, that increase ceramide/S1P ratio, downregulated S1PR expression and blocked BRAFi-resistant melanoma cell growth. This effect was associated with a decreased expression of MITF and Bcl-2. Moreover, the BH3 mimetic ABT-737 improved the antitumor activity of approaches targeting S1P-metabolizing enzymes in BRAFiresistant melanoma cells. Collectively, our findings indicate that targeting the S1P/S1PR axis could provide effective therapeutic options for patients with melanoma who relapse after BRAFi therapy.

Research paper thumbnail of New markers for early detection of acute kidney injury after transcatheter aortic valve implantation

Anaesthesia, critical care & pain medicine, Jan 13, 2017

Acute Kidney Injury (AKI) is a frequent complication after a Transcatheter Aortic Valve Implantat... more Acute Kidney Injury (AKI) is a frequent complication after a Transcatheter Aortic Valve Implantation (TAVI). Biomarkers such as urinary G1 cell cycle arrest proteins (TIMP-2 and IGFBP7) and sonographic evaluation (Doppler Renal Resistive Index (RRI)) have been advocated to predict AKI at an early stage after a TAVI-procedure. The primary aim was to determine the predictive value of these markers to detect AKI after a TAVI-procedure at an early phase. In a prospective observational study, 62 consecutive patients were scheduled for a TAVI. AKI was assessed based on the KDIGO criteria. Biomarkers and RRI were measured concomitantly before TAVI, at the first micturition post-implantation and the first micturition on the morning after the procedure. Twenty-two patients (35%) developed AKI. On the first day after the TAVI-procedure, Urinary TIMP-2 and IGFBP7 concentrations increased significantly in patients who developed AKI (0.1, [interquartile] [0.1-0.35] to 0.40 [0.10-1.00] vs 0.2 [0....

Research paper thumbnail of Impact of albumin assays in the diagnosis of malnutrition in hemodialysis patients: a cohort study

Journal of Renal Nutrition

Research paper thumbnail of PHACTR-1 (Phosphatase and Actin Regulator 1) Deficiency in Either Endothelial or Smooth Muscle Cells Does Not Predispose Mice to Nonatherosclerotic Arteriopathies in 3 Transgenic Mice

Arteriosclerosis, Thrombosis, and Vascular Biology

Background: Genome-wide association studies have revealed robust associations of common genetic p... more Background: Genome-wide association studies have revealed robust associations of common genetic polymorphisms in an intron of the PHACTR-1 (phosphatase and actin regulator 1) gene (chr6p24), with cervical artery dissection, spontaneous coronary artery dissection, and fibromuscular dysplasia. The aim was to assess its role in the pathogenesis of cervical artery dissection or fibromuscular dysplasia. Methods: Using various tissue-specific Cre-driver mouse lines, Phactr1 was deleted either in endothelial cells using 2 tissue-specific Cre-driver (PDGFB [platelet-derived growth factor B]-Cre ERT2 mice and Tie2 [tyrosine kinase with immunoglobulin and EGF homology domains]-Cre) and smooth muscle cells (smooth muscle actin-Cre ERT2 ) with a third tissue-specific Cre-driver. Results: To test the efficacy of the Phactr1 deletion after cre-induction, we confirmed first, a decrease in Phactr1 transcription and Phactr1 expression in endothelial cell and smooth muscle cell isolated from Phactr1 ...

Research paper thumbnail of Increased Capillary Permeability in Heart Induces Diastolic Dysfunction Independently of Inflammation, Fibrosis, or Cardiomyocyte Dysfunction

Arteriosclerosis, Thrombosis, and Vascular Biology

Background: While endothelial dysfunction is suggested to contribute to heart failure with preser... more Background: While endothelial dysfunction is suggested to contribute to heart failure with preserved ejection fraction pathophysiology, understanding the importance of the endothelium alone, in the pathogenesis of diastolic abnormalities has not yet been fully elucidated. Here, we investigated the consequences of specific endothelial dysfunction on cardiac function, independently of any comorbidity or risk factor (diabetes or obesity) and their potential effect on cardiomyocyte. Methods: The ubiquitine ligase Pdzrn3 , expressed in endothelial cells (ECs), was shown to destabilize tight junction. A genetic mouse model in which Pdzrn3 is overexpressed in EC (iEC-Pdzrn3) in adults was developed. Results: EC-specific Pdzrn3 expression increased cardiac leakage of IgG and fibrinogen blood-born molecules. The induced edema demonstrated features of diastolic dysfunction, with increased end-diastolic pressure, alteration of dP/dt min, increased natriuretic peptides, in addition to limited e...

Research paper thumbnail of ROR2 in post-natal vessel formation

Archives of Cardiovascular Diseases Supplements, 2018

Research paper thumbnail of Plasma creatinine below limit of quantification in a patient with acute kidney injury

Clinica Chimica Acta, 2022

Acute kidney injury (AKI) is an infrequent complication of inflammatory bowel disease and can be ... more Acute kidney injury (AKI) is an infrequent complication of inflammatory bowel disease and can be exceptionally linked to interstitial nephritis secondary to anti-inflammatory drugs, such as Pentasa® (5-ASA). Case presentation We present an case of an 80-year-old man who presented chronic diarrheas treated by Pentasa®. He developed AKI, evidenced by high plasma creatinine dosed in his local laboratory. At the hospital admission, plasma creatinine was exceptionally undetectable by the enzymatic method while Jaffe's method successfully determined it. Creatinine measurement by the enzymatic method was gradually restored during hospital stay, concomitant with the discontinuation of 5-ASA administration, suggesting that this drug could interfere with creatinine enzymatic assay. Creatinine enzymatic assays combine serial reactions. The last one called Trinder reaction, catalyzed by a peroxidase, uses H2O2 to convert uncolored dye in a colored compound, proportionally to creatinine concentration. We showed that AKI related-plasma accumulation of 5-ASA, could participate in the negative interference observed on creatinine measurement, by scavenging H2O2. Interestingly, all Trinder reaction-based measurements (uric acid, lipase, lactate, triglycerides and cholesterol) were affected. Negative interference of 5-ASA was confirmed by interferogram experiments on all Trinder reaction-dependent assays. All Trinder-dependent parameters should be interpreted with the patient's treatment knowledge, in particular salicylate derivatives.

Research paper thumbnail of No direct involvement of Phactr-1 in non-atherosclerotic arteriopathies: results from 3 different Phactr-1 transgenic knockout mice

European Heart Journal, 2021

Introduction Genome-wide association studies have revealed robust associations of common genetic ... more Introduction Genome-wide association studies have revealed robust associations of common genetic polymorphisms in the Phactr1 locus (6p24) (encoding Phosphatase and Actin Regulator 1) with cervico-cerebral artery dissection (CCeAD), spontaneous coronary artery dissection (SCAD) and fibromuscular dysplasia (FMD). These common elements of genetic predisposition provide a proof of concept for important shared mechanisms at the molecular level between CCeAD, SCAD and FMD vascular diseases. Objective Deciphering genetic, molecular and physiological importance of PHACTR1. Method Using various tissue-specific Cre-driver mouse lines, Phactr1 was deleted either in endothelial cells (EC) using 2 tissue-specific Cre-driver (one of them was embryonic) and Smooth Muscle Cells (SMC) with a third tissue-specific Cre-driver to assess its role in the pathogenesis of CCeAD, SCAD or FMD. Results To test the efficacy of the Phactr1 deletion after cre-induction, we confirmed firstly, a decrease in Phact...

Research paper thumbnail of Wnt/frizzled Signaling in Endothelium: A Major Player in Blood-Retinal- and Blood-Brain-Barrier Integrity

Cold Spring Harbor Perspectives in Medicine, 2022

The Wnt/frizzled signaling pathway is one of the major regulators of endothelial biology, control... more 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 pathways: the canonical Wnt/β-catenin signaling pathway whose main downstream effector is the transcriptional coactivator β-catenin, and the noncanonical Wnt signaling pathway, which is subdivided into the Wnt/Ca2+ pathway and the planar cell polarity pathway. Here, we will focus on its cross talk with other angiogenic pathways and on its role in blood-retinal- and blood-brain-barrier formation and its maintenance in a differentiated state. We will unravel how retinal vascular pathologies and neurovascular degenerative diseases result from disruption of the Wnt pathway related to vascular instability, and highlight current research into therapeutic options.

Research paper thumbnail of Article original Acidose lactique et interférence analytique lors du dosage de l'éthylène glycol selon une méthode colorimétrique : à propos d'un cas Analytical interference between lactates and ethylene glycol: a case report

Research paper thumbnail of Abrogating Frizzled7 in endothelial cell protects against the development of pathological angiogenesis during proliferative retinopathy

Archives of Cardiovascular Diseases Supplements

Research paper thumbnail of Pigments test strips: A rapid companion test to exclude sub-arachnoid haemorrhage

Research paper thumbnail of Mast Cells Are the Trigger of Small Vessel Disease and Diastolic Dysfunction in Diabetic Obese Mice

Arteriosclerosis, Thrombosis, and Vascular Biology

Objective: Heart failure with preserved ejection fraction is a major health care issue which has ... more Objective: Heart failure with preserved ejection fraction is a major health care issue which has been difficult to manage to date, due to its complex and not well understood pathophysiology. Specifically, if a wealth of literature focuses on heart failure with preserved ejection fraction cardiac component, very little information can be found on its vascular component. Our goal is to unravel the critical role of cardiac small vessel disease in the pathophysiology of diastolic dysfunction. Approach and Results: To do so, we used leptin receptor deficient (Lepr db/db ) female mice, a recognized model of diastolic dysfunction. In these mice, the increased end-diastolic pressure signing diastolic dysfunction is associated with vascular leakage, endothelial cell activation, and leucocyte infiltration. Strikingly, a RNA sequencing analysis of the cardiac vascular fraction of both Lepr db/db and control mice confirmed endothelial dysfunction and systemic inflammation, but above all, reveal...

Research paper thumbnail of Covichem: A biochemical severity risk score of COVID-19 upon hospital admission

PLOS ONE

Clinical and laboratory predictors of COVID-19 severity are now well described and combined to pr... more Clinical and laboratory predictors of COVID-19 severity are now well described and combined to propose mortality or severity scores. However, they all necessitate saturable equipment such as scanners, or procedures difficult to implement such as blood gas measures. To provide an easy and fast COVID-19 severity risk score upon hospital admission, and keeping in mind the above limits, we sought for a scoring system needing limited invasive data such as a simple blood test and co-morbidity assessment by anamnesis. A retrospective study of 303 patients (203 from Bordeaux University hospital and an external independent cohort of 100 patients from Paris Pitié-Salpêtrière hospital) collected clinical and biochemical parameters at admission. Using stepwise model selection by Akaike Information Criterion (AIC), we built the severity score Covichem. Among 26 tested variables, 7: obesity, cardiovascular conditions, plasma sodium, albumin, ferritin, LDH and CK were the independent predictors of...

Research paper thumbnail of Mast cells participate in the development of diastolic dysfunction in diabetic obese mice

RationalHeart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic issue. ... more RationalHeart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic issue. However, to date, its pathophysiology remains poorly understood.ObjectiveOur goal was to investigate the role of microvessel disease in the pathophysiology of diastolic dysfunction.FindingsTo do so, we used Leptin receptor deficient (Leprdb/db) female mice as a model of diastolic dysfunction. In these mice, the increased end diastolic pressure (EDP) signing diastolic dysfunction is associated with vascular leakage, endothelial cell activation and leucocyte infiltration. Strikingly, a RNA sequencing analysis of the cardiac vascular fraction of both Leprdb/db and control female mice confirmed endothelial dysfunction and systemic inflammation but also revealed a strong increase in several mast cell markers (notably FceR1a, Tryptase and Chymase). We then histologically confirmed an accumulation of activated mast cells in the heart of Leprdb/db mice. Importantly, mast cell degranulation inhib...

Research paper thumbnail of Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019

Clinical Kidney Journal

Background Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, se... more Background Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported. Methods Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated. Results Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12–23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35...

Research paper thumbnail of Characterisation of Acute Kidney Injury in Critically Ill Patients with Severe Coronavirus Disease-2019 (COVID-19)

Background: COVID19-associated acute kidney injury frequency, severity and characterisation in cr... more Background: COVID19-associated acute kidney injury frequency, severity and characterisation in critically ill patients has not been reported. Methods: Single-center cohort performed from March 3, 2020, to April 14, 2020 in 4 intensive care units in Bordeaux University Hospital, France. All patients with COVID19 and pulmonary severity criteria were included. AKI was defined using KDIGO criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterisation (transient vs. persistent acute kidney injury; proteinuria, hematuria and glycosuria), and short-term outcomes was evaluated. Results: 71 patients were included, with basal serum creatinine of 69 +/- 21 micromol/L. At admission, AKI was present in 8/71 (11%) patients. Median follow-up was 17 [12-23] days. AKI developed in a total of 57/71 (80%) patients with 35% Stage 1, 35% Stage 2, and 30% Stage 3 acute kidney injury; 10/57 (18%) required renal replacement therapy. Transi...

Research paper thumbnail of Therapies targeting Frizzled‐7/β‐catenin pathway prevent the development of pathological angiogenesis in an ischemic retinopathy model

Research paper thumbnail of Comparison of endothelial promoter efficiency and specificity in mice reveals a subset of Pdgfb‐positive hematopoietic cells

Journal of Thrombosis and Haemostasis

Research paper thumbnail of A combined approach for the early recognition of acute kidney injury after adult cardiac surgery

Anaesthesia Critical Care & Pain Medicine

Research paper thumbnail of Targeting the sphingosine 1-phosphate axis exerts potent antitumor activity in BRAFi-resistant melanomas

Molecular Cancer Therapeutics

BRAF inhibitors (BRAFi) are used to treat patients with melanoma harboring the V600E mutation. Ho... more BRAF inhibitors (BRAFi) are used to treat patients with melanoma harboring the V600E mutation. However, resistance to BRAFi is inevitable. Here, we identified sphingosine 1-phosphate (S1P) receptors as regulators of BRAF V600Emutant melanoma cell-autonomous resistance to BRAFi. Moreover, our results reveal a distinct sphingolipid profile, that is, a tendency for increased very long-chain ceramide species, in the plasma of patients with melanoma who achieve a response to BRAFi therapy as compared with patients with progressive disease. Treatment with BRAFi resulted in a strong decrease in S1PR1/3 expression in sensitive but not in resistant cells. Genetic and pharmacologic interventions, that increase ceramide/S1P ratio, downregulated S1PR expression and blocked BRAFi-resistant melanoma cell growth. This effect was associated with a decreased expression of MITF and Bcl-2. Moreover, the BH3 mimetic ABT-737 improved the antitumor activity of approaches targeting S1P-metabolizing enzymes in BRAFiresistant melanoma cells. Collectively, our findings indicate that targeting the S1P/S1PR axis could provide effective therapeutic options for patients with melanoma who relapse after BRAFi therapy.

Research paper thumbnail of New markers for early detection of acute kidney injury after transcatheter aortic valve implantation

Anaesthesia, critical care & pain medicine, Jan 13, 2017

Acute Kidney Injury (AKI) is a frequent complication after a Transcatheter Aortic Valve Implantat... more Acute Kidney Injury (AKI) is a frequent complication after a Transcatheter Aortic Valve Implantation (TAVI). Biomarkers such as urinary G1 cell cycle arrest proteins (TIMP-2 and IGFBP7) and sonographic evaluation (Doppler Renal Resistive Index (RRI)) have been advocated to predict AKI at an early stage after a TAVI-procedure. The primary aim was to determine the predictive value of these markers to detect AKI after a TAVI-procedure at an early phase. In a prospective observational study, 62 consecutive patients were scheduled for a TAVI. AKI was assessed based on the KDIGO criteria. Biomarkers and RRI were measured concomitantly before TAVI, at the first micturition post-implantation and the first micturition on the morning after the procedure. Twenty-two patients (35%) developed AKI. On the first day after the TAVI-procedure, Urinary TIMP-2 and IGFBP7 concentrations increased significantly in patients who developed AKI (0.1, [interquartile] [0.1-0.35] to 0.40 [0.10-1.00] vs 0.2 [0....