A5032985944- Pulmonary Hypertension Research and Treatments
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cardiovascular Issues in Pregnancy
- Eosinophilic Disorders and Syndromes
- Cardiovascular Function and Risk Factors
- Nitric Oxide and Endothelin Effects
- Renin-Angiotensin System Studies
- Chronic Myeloid Leukemia Treatments
- Vascular Anomalies and Treatments
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Systemic Sclerosis and Related Diseases
- Eicosanoids and Hypertension Pharmacology
- Macrophage Migration Inhibitory Factor
- Transplantation: Methods and Outcomes
- PI3K/AKT/mTOR signaling in cancer
- Neonatal Respiratory Health Research
- Medical Imaging and Pathology Studies
- Liver Disease and Transplantation
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Peptidase Inhibition and Analysis
- Cardiomyopathy and Myosin Studies
- Heart Failure Treatment and Management
- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Organ Transplantation Techniques and Outcomes
Inserm
2016-2025
Université Paris-Saclay
2016-2025
Hypertension pulmonaire : physiopathologie et innovation thérapeutique
2013-2025
Hôpital Marie Lannelongue
2015-2024
Bicêtre Hospital
2012-2024
AR2i
2012-2024
Université Paris-Sud
2013-2023
Centre Chirurgical Marie Lannelongue
2009-2023
Assistance Publique – Hôpitaux de Paris
2006-2023
Hôpital Paris Saint-Joseph
2020-2023
The French pulmonary hypertension (PH) registry allows the survey of epidemiological trends. Isolated cases precapillary PH have been reported in patients who chronic myelogenous leukemia treated with tyrosine kinase inhibitor dasatinib.This study was designed to describe incident dasatinib-associated registry. From approval dasatinib (November 2006) September 30, 2010, 9 by at time diagnosis were identified. At diagnosis, had moderate severe functional and hemodynamic impairment. No other...
Loss-of-function mutations in bone morphogenetic protein receptor II (BMP-RII) are linked to pulmonary arterial hypertension (PAH); the ligand for BMP-RII, BMP-2, is a negative regulator of SMC growth. Here, we report an interplay between PPARgamma and its transcriptional target apoE downstream BMP-2 signaling. BMP-2/BMP-RII signaling prevented PDGF-BB-induced proliferation human murine artery SMCs (PASMCs) by decreasing nuclear phospho-ERK inducing DNA binding that independent Smad1/5/8...
Patients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems such as the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous are up-regulated, but this may long-term negative effects on progression of iPAH.
Background— The role of right ventricular (RV) diastolic stiffness in pulmonary arterial hypertension (PAH) is not well established. Therefore, we investigated the presence and possible underlying mechanisms RV PAH patients. Methods Results— Single-beat pressure-volume analyses were performed 21 patients 7 control subjects to study stiffness. Data are presented as mean±SEM. (β) was significantly increased (PAH, 0.050±0.005 versus control, 0.029±0.003; P <0.05) closely associated with...
Pulmonary arterial hypertension (PAH) is a life-threatening disease that can be induced by dasatinib, dual Src and BCR-ABL tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML). Today, key questions remain regarding the mechanisms involved in long-term development of dasatinib-induced PAH. Here, we demonstrated dasatinib therapy causes pulmonary endothelial damage humans rodents. We found treatment attenuated hypoxic vasoconstriction responses increased susceptibility...
Pericytes and their crosstalk with endothelial cells are critical for the development of a functional microvasculature vascular remodeling. It is also known that pulmonary dysfunction intertwined initiation progression arterial hypertension (PAH). We hypothesized dysfunction, characterized by abnormal fibroblast growth factor-2 interleukin-6 signaling, leads to microvascular pericyte coverage causing medial thickening.In human lung tissues, numbers pericytes substantially increased (up...
Background— The mechanism of pulmonary artery smooth muscle cell (PA-SMC) hyperplasia in idiopathic hypertension (iPH) may involve both an inherent characteristic PA-SMCs and abnormal control by external stimuli. We investigated the role microvascular endothelial cells (P-ECs) controlling PA-SMC growth. Methods Results— Serum-free medium quiescent P-ECs elicited marked proliferation, this effect was greater with from patients iPH than subjects these subjects. Fluoxetine, which inhibits...
Pulmonary arterial remodeling characterized by increased vascular smooth muscle density is a common lesion seen in pulmonary hypertension (PAH), deadly condition. Clinical correlation studies have suggested an immune pathogenesis of remodeling, but experimental proof has been lacking. We show that immunization and prolonged intermittent challenge via the airways with either two different soluble antigens induced severe muscularization small- to medium-sized arteries. Depletion CD4+ T cells,...
Background— Progression of pulmonary hypertension (PH) is associated with increased lung expression the serotonin transporter (5-HTT), which leads to hyperplasia artery smooth muscle cells (PA-SMCs). Given postulated causal relation between 5-HTT overexpression and PH, we herein investigated whether highly selective inhibitor fluoxetine prevented and/or reversed PH induced by monocrotaline (MCT) in rats. Selective 5-HT 1B/1D , 2A 2B receptor antagonists were used for comparative testing....
Pulmonary hypertension (PH) is a progressive, lethal lung disease characterized by pulmonary artery SMC (PA-SMC) hyperplasia leading to right-sided heart failure. Molecular events originating in ECs (P-ECs) may contribute the PA-SMC PH. Thus, we exposed cultured human medium conditioned P-EC from patients with idiopathic PH (IPH) or controls and found that IPH P-EC–conditioned increased proliferation more than control medium. Levels of FGF2 were P-ECs over controls, while there was no...
One intrinsic abnormality of pulmonary artery smooth muscle cells (PA-SMCs) in human idiopathic hypertension (iPH) is an exaggerated proliferative response to internalized serotonin (5-HT) caused by increased expression the 5-HT transporter (5-HTT). To investigate whether 5-HTT overexpression PA-SMCs sufficient produce PH, we generated transgenic mice overexpressing under control SM22 promoter. Studies SM22-LacZ(+) showed that transgene was expressed predominantly SMCs and systemic vessels....
Inflammation and endothelial dysfunction are considered two primary instigators of pulmonary arterial hypertension (PAH). CD74 is a receptor for the proinflammatory cytokine macrophage migration inhibitory factor (MIF). This ligand/receptor complex initiates survival pathways cell proliferation, it triggers synthesis secretion major factors adhesion molecules.We hypothesized that MIF/CD74 signaling pathway overexpressed in idiopathic PAH (iPAH) contributes to (EC) phenotype.Primary early...
Rationale: The complex and multifactorial pathogenesis of pulmonary hypertension (PH) involves constriction, remodeling, in situ thrombosis vessels. Both serotonin (5-HT) Rho kinase signaling may contribute to these alterations.Objectives: To investigate possible links between the 5-HT transporter (5-HTT) RhoA/Rho pathways, as well their involvement progression human experimental PH.Methods: Biochemical functional analyses lungs, platelets, artery smooth muscle cells (PA-SMCs) from patients...