The Experts below are selected from a list of 18033 Experts worldwide ranked by ideXlab platform

S.m. Kanse - One of the best experts on this subject based on the ideXlab platform.

Marc Humbert - One of the best experts on this subject based on the ideXlab platform.

  • Endothelin Receptor antagonists.
    Handbook of Experimental Pharmacology, 2013
    Co-Authors: Martine Clozel, Alessandro Maresta, Marc Humbert
    Abstract:

    Three pathways have been identified in the pathogenesis of pulmonary arterial hypertension (PAH): the Endothelin (ET), nitric oxide (NO) and prostacyclin pathways. These pathways represent the targets of approved PAH therapies and their discovery has facilitated significant progress in the understanding and treatment of PAH. The ET system is well established as a key player in the pathophysiology of PAH, with deleterious effects mediated by both the ETA and ETB Receptors. Endothelin Receptor antagonists (ERAs) are an important part of PAH therapy, with two ERAs currently approved for the treatment of PAH and a novel ERA that has recently been investigated in a Phase III clinical trial. This chapter describes the role of ET in the pathogenesis of PAH, reviews experimental data and examines the clinical status of ERAs in PAH treatment.

  • Endothelin Receptor antagonists for the treatment of pulmonary arterial hypertension.
    Expert Opinion on Pharmacotherapy, 2011
    Co-Authors: Dermot S. O'callaghan, Marc Humbert, Laurent Savale, Azzedine Yaici, Delphine Natali, Xavier Jaïs, Florence Parent, David Montani, Gérald Simonneau, Olivier Sitbon
    Abstract:

    Introduction: Endothelin is a key mediator in the pathophysiology of pulmonary arterial hypertension (PAH). Its effects are mediated through the activation of two associated Receptor subtypes, termed A and B. Therapeutic strategies that modulate the activity of Endothelin are, therefore, of interest to improve the functional status of patients with PAH. Areas covered: The rationale for the use of Endothelin Receptor antagonists as a therapeutic class in PAH and pertinent data from important clinical studies are presented in this review. Areas for future research are also suggested. Expert opinion: The availability of the Endothelin Receptor antagonist class of agents represents a significant addition to the therapeutic armamentarium which is available for the treatment of PAH. Comparative studies are warranted to establish whether selective Endothelin-A Receptor antagonism is more advantageous than dual Receptor antagonism. Future studies of Endothelin Receptor antagonists will increasingly focus on the p...

  • Drug Insight: Endothelin-Receptor antagonists for pulmonary arterial hypertension in systemic rheumatic diseases
    Nature Clinical Practice Rheumatology, 2005
    Co-Authors: Marc Humbert, Gérald Simonneau
    Abstract:

    Pulmonary arterial hypertension (PAH) describes a group of diseases characterized by raised pulmonary arterial pressure and obstruction of small precapillary pulmonary arteries leading to right-heart failure PAH can occur as a devastating complication in patients with systemic sclerosis Various treatment approaches for PAH have been investigated, including Endothelin-Receptor antagonists Data support the use of the oral dual Endothelin-Receptor antagonist bosentan in stabilizing or improving exercise capacity in patients with PAH associated with systemic sclerosis More information on long-term therapy is needed in order to evaluate long-term outcome in this difficult-to-treat population Oral bosentan at a dose of 125 mg twice daily is approved for treatment of PAH in many countries, including North America and Europe Monthly monitoring of liver function tests is mandatory in bosentan-treated patients because of the possible elevation of hepatic aminotransferase levels Pulmonary arterial hypertension is particularly common in individuals with systemic sclerosis, but is also seen in other rheumatic diseases. A number of treatment optionsfor this serious complication are available, including selective and unselective Endothelin-Receptor antagonists, which are the subject of this review. Rapid advances in the understanding of Endothelin as a naturally occurring peptide with developmental and regulatory roles in normal physiology, along with a number of deleterious effects under pathologic conditions (including vasoconstriction, fibrosis, vascular hypertrophy, and inflammation) have led to the development of Endothelin-Receptor antagonists (ERAs). Bosentan, an antagonist with dual specificity for the Endothelin-Receptor subtypes A and B, has been shown to be efficacious and well tolerated in placebo-controlled clinical trials and is now approved in many countries, including the US, Canada, and Europe, for treatment of pulmonary arterial hypertension (PAH), including PAH associated with rheumatic diseases. ERAs with specificity for the Endothelin-Receptor subtype A, including sitaxsentan and ambrisentan, are currently undergoing investigation. This article reviews PAH associated with systemic rheumatic diseases and describes the role of ERAs in this setting.

  • Drug Insight: Endothelin-Receptor antagonists for pulmonary arterial hypertension in systemic rheumatic diseases.
    Nature clinical practice. Rheumatology, 2005
    Co-Authors: Marc Humbert, Gérald Simonneau
    Abstract:

    Rapid advances in the understanding of Endothelin as a naturally occurring peptide with developmental and regulatory roles in normal physiology, along with a number of deleterious effects under pathologic conditions (including vasoconstriction, fibrosis, vascular hypertrophy, and inflammation) have led to the development of Endothelin-Receptor antagonists (ERAs). Bosentan, an antagonist with dual specificity for the Endothelin-Receptor subtypes A and B, has been shown to be efficacious and well tolerated in placebo-controlled clinical trials and is now approved in many countries, including the US, Canada, and Europe, for treatment of pulmonary arterial hypertension (PAH), including PAH associated with rheumatic diseases. ERAs with specificity for the Endothelin-Receptor subtype A, including sitaxsentan and ambrisentan, are currently undergoing investigation. This article reviews PAH associated with systemic rheumatic diseases and describes the role of ERAs in this setting.

Christian Ruiz - One of the best experts on this subject based on the ideXlab platform.

  • Endothelin Receptor type b counteracts tenascin c induced Endothelin Receptor type a dependent focal adhesion and actin stress fiber disorganization
    Cancer Research, 2007
    Co-Authors: Katrin Lange, Martial Kammerer, Monika E Hegi, Stefan Grotegut, Antje Dittmann, Wentao Huang, Erika Fluri, George W Yip, Martin Gotte, Christian Ruiz
    Abstract:

    Tenascin-C, an extracellular matrix molecule of the tumor-specific microenvironment, counteracts the tumor cell proliferation-suppressing effect of fibronectin by blocking the integrin alpha(5)beta(1)/syndecan-4 complex. This causes cell rounding and stimulates tumor cell proliferation. Tenascin-C also stimulates Endothelin Receptor type A (EDNRA) expression. Here, we investigated whether signaling through Endothelin Receptors affects tenascin-C-induced cell rounding. We observed that Endothelin Receptor type B (EDNRB) activation inhibited cell rounding by tenascin-C and induced spreading by restoring expression and function of focal adhesion kinase (FAK), paxillin, RhoA, and tropomyosin-1 (TM1) via activation of epidermal growth factor Receptor, phospholipase C, c-Jun NH(2)-terminal kinase, and the phosphatidylinositol 3-kinase pathway. In contrast to EDNRB, signaling through EDNRA induced cell rounding, which correlated with FAK inhibition and TM1 and RhoA protein destabilization in the presence of tenascin-C. This occurred in a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-dependent manner. Thus, tumorigenesis might be enhanced by tenascin-C involving EDNRA signaling. Inhibition of tenascin-C in combination with blocking both Endothelin Receptors could present a strategy for sensitization of cancer and endothelial cells toward anoikis.

  • Endothelin Receptor Type B Counteracts Tenascin-C–Induced Endothelin Receptor Type A–Dependent Focal Adhesion and Actin Stress Fiber Disorganization
    Cancer research, 2007
    Co-Authors: Katrin Lange, Martial Kammerer, Monika E Hegi, Stefan Grotegut, Antje Dittmann, Wentao Huang, Erika Fluri, George W Yip, Martin Gotte, Christian Ruiz
    Abstract:

    Tenascin-C, an extracellular matrix molecule of the tumor-specific microenvironment, counteracts the tumor cell proliferation-suppressing effect of fibronectin by blocking the integrin alpha(5)beta(1)/syndecan-4 complex. This causes cell rounding and stimulates tumor cell proliferation. Tenascin-C also stimulates Endothelin Receptor type A (EDNRA) expression. Here, we investigated whether signaling through Endothelin Receptors affects tenascin-C-induced cell rounding. We observed that Endothelin Receptor type B (EDNRB) activation inhibited cell rounding by tenascin-C and induced spreading by restoring expression and function of focal adhesion kinase (FAK), paxillin, RhoA, and tropomyosin-1 (TM1) via activation of epidermal growth factor Receptor, phospholipase C, c-Jun NH(2)-terminal kinase, and the phosphatidylinositol 3-kinase pathway. In contrast to EDNRB, signaling through EDNRA induced cell rounding, which correlated with FAK inhibition and TM1 and RhoA protein destabilization in the presence of tenascin-C. This occurred in a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-dependent manner. Thus, tumorigenesis might be enhanced by tenascin-C involving EDNRA signaling. Inhibition of tenascin-C in combination with blocking both Endothelin Receptors could present a strategy for sensitization of cancer and endothelial cells toward anoikis.

Michel Burnier - One of the best experts on this subject based on the ideXlab platform.

  • Update on Endothelin Receptor Antagonists in Hypertension.
    Current Hypertension Reports, 2018
    Co-Authors: Michel Burnier
    Abstract:

    Purpose of Review To review the most recent data on the development of Endothelin Receptor antagonists (ERAs) for the treatment of hypertension and the management of diabetic nephropathy

  • Update on Endothelin Receptor Antagonists in Hypertension
    Current Hypertension Reports, 2018
    Co-Authors: Michel Burnier
    Abstract:

    Purpose of Review To review the most recent data on the development of Endothelin Receptor antagonists (ERAs) for the treatment of hypertension and the management of diabetic nephropathy Recent Findings Recent reviews and meta-analyses of experimental and clinical data obtained with ERAs confirmed that Endothelin Receptor blockade is associated with significant decreases in blood pressure in essential hypertension but also in resistant hypertension. In addition, in patients with diabetic nephropathy, ERAs induce significant 30–40% decreases in albuminuria when administered on top of blockers of the renin-angiotensin system. Yet, the benefits of ERAs have often been limited by their tolerability profile, essentially fluid retention and the development of edema and liver toxicity. Hence, several programs have been interrupted. Today, only one ERA, aprocitentan, is still under development for the treatment of resistant hypertension. Regarding the place of ERAs in the management of diabetic nephropathy, the results of the SONAR trial with atrasentan are eagerly awaited but the recent interruption of this trial because of insufficient events is worrisome, as one might not obtain all the expected information for this major trial. Summary Blockade of Endothelin Receptor have a high potential in the treatment of hypertension and the prevention of the progression of renal diseases such as diabetic nephropathy. Today, the number of clinical programs investigating the potential benefits of ERAs is limited and more data must be obtained to define the real place of ERAs in these indications.

P. Newman - One of the best experts on this subject based on the ideXlab platform.