Endothelin-receptor antagonists in the management of pulmonary arterial hypertension: where do we stand?

Correale, Michele; Ferraretti, Armando; Monaco, Ilenia; Grazioli, Davide; Brunetti, Natale Daniele

doi:10.2147/vhrm.s133921

Cited by 38 publications

(46 citation statements)

References 71 publications

(81 reference statements)

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“…Endothelin receptor blockade (either unselective or ETA‐specific) is an established therapy for pulmonary hypertension and may have anti‐tumor activity in the case of ETB . According to our results, such therapy may impact on FGF23 and mineral metabolism.…”

Section: Discussionmentioning

confidence: 58%

Endothelin receptor B controls the production of fibroblast growth factor 23

et al. 2020

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Endothelin-1 (ET-1) is a member of the endothelin family of peptide hormones first discovered as endothelium-derived mediators regulating vascular tone. ET-1 also regulates the proliferation and differentiation of bone cells that synthesize fibroblast growth factor 23 (FGF23). FGF23 is a hormone controlling renal phosphate and vitamin D metabolism. Here, we studied the role of ET-1 and endothelin receptor B (ETB) for FGF23 production. Fgf23 gene expression was studied in IDG-SW3 bone cells by quantitative RT-PCR. ETB-expressing (etb +/+ ) and rescued ETBdeficient mice (etb −/− ) were studied in metabolic cages. Their serum FGF23, PTH, and 1,25(OH) 2 D 3 concentrations were determined by ELISA, serum and urinary phosphate and Ca 2+ by photometric methods. ET-1 and ETB agonist sarafotoxin 6c suppressed Fgf23 mRNA in IDG-SW3 cells. Serum C-terminal and intact FGF23 as well as bone Fgf23 mRNA levels were significantly higher in etb −/− mice than in etb +/+ mice. Renal phosphate excretion was significantly higher in etb −/− mice despite lower phosphate levels. In addition, etb −/− animals exhibited calciuria and a significantly higher serum 1,25(OH) 2 D 3 concentration compared to etb +/+ mice. In conclusion, ETB-dependent ET-1 signaling is a potent suppressor of FGF23 formation. This effect is likely to be of clinical relevance given the use of endothelin receptor antagonists in various diseases. K E Y W O R D SET-1, klotho, phosphate, vitamin D

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Section: Discussionmentioning

confidence: 58%

Endothelin receptor B controls the production of fibroblast growth factor 23

et al. 2020

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“…Endothelin is a polypeptide that is produced by the vascular endothelium. Endothelin is a potent vasoconstrictor that induces vascular smooth muscle proliferation and in patients with PAH, high plasma levels of endothelin-1 (ET-1) have been documented due to an increase in production in endothelial cells and decreased elimination of ET-1 in lung [133]. Currently, endothelin receptor antagonists (ERAs) are approved for treatment in pulmonary arterial hypertension by demonstrating efficacy in PAH (Seraphin, ARIES and Breathe trials).…”

Section: Endothelinmentioning

confidence: 99%

Emerging Mechanisms of Pulmonary Vasoconstriction in SARS-CoV-2-Induced Acute Respiratory Distress Syndrome (ARDS) and Potential Therapeutic Targets

Karmouty‐Quintana

Thandavarayan

Keller

et al. 2020

IJMS

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The 1918 influenza killed approximately 50 million people in a few short years, and now, the world is facing another pandemic. In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of a respiratory illness termed coronavirus disease 2019 (COVID-19) and rapidly spread to cause the worst pandemic since 1918. Recent clinical reports highlight an atypical presentation of acute respiratory distress syndrome (ARDS) in COVID-19 patients characterized by severe hypoxemia, an imbalance of the renin–angiotensin system, an increase in thrombogenic processes, and a cytokine release storm. These processes not only exacerbate lung injury but can also promote pulmonary vascular remodeling and vasoconstriction, which are hallmarks of pulmonary hypertension (PH). PH is a complication of ARDS that has received little attention; thus, we hypothesize that PH in COVID-19-induced ARDS represents an important target for disease amelioration. The mechanisms that can promote PH following SARS-CoV-2 infection are described. In this review article, we outline emerging mechanisms of pulmonary vascular dysfunction and outline potential treatment options that have been clinically tested.

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“…We refer readers to the following excellent review articles summarizing clinical trials with GPCR agonists or/and antagonists in PH patients including endothelin receptor antagonists (204), prostacyclin receptors agonists (205), and beta-blockers (206). Here we briefly discuss clinical studies evaluating the effects of above-mentioned drugs on the RV in PH patients.…”

Section: Role Of Gpcrs In Rv Remodeling and Dysfunctionmentioning

confidence: 99%

The Role of G Protein-Coupled Receptors in the Right Ventricle in Pulmonary Hypertension

Viswanathan

Mamazhakypov

Schermuly

et al. 2018

Front. Cardiovasc. Med.

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Pressure overload of the right ventricle (RV) in pulmonary arterial hypertension (PAH) leads to RV remodeling and failure, an important determinant of outcome in patients with PAH. Several G protein-coupled receptors (GPCRs) are differentially regulated in the RV myocardium, contributing to the pathogenesis of RV adverse remodeling and dysfunction. Many pharmacological agents that target GPCRs have been demonstrated to result in beneficial effects on left ventricular (LV) failure, such as beta-adrenergic receptor and angiotensin receptor antagonists. However, the role of such drugs on RV remodeling and performance is not known at this time. Moreover, many of these same receptors are also expressed in the pulmonary vasculature, which could result in complex effects in PAH. This manuscript reviews the role of GPCRs in the RV remodeling and dysfunction and discusses activating and blocking GPCR signaling to potentially attenuate remodeling while promoting improvements of RV function in PAH.

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Endothelin-receptor antagonists in the management of pulmonary arterial hypertension: where do we stand?

Cited by 38 publications

References 71 publications

Endothelin receptor B controls the production of fibroblast growth factor 23

Endothelin receptor B controls the production of fibroblast growth factor 23

Emerging Mechanisms of Pulmonary Vasoconstriction in SARS-CoV-2-Induced Acute Respiratory Distress Syndrome (ARDS) and Potential Therapeutic Targets

The Role of G Protein-Coupled Receptors in the Right Ventricle in Pulmonary Hypertension

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