08 October 2018

This week in PVD

A sample of the latest PH news output from around the web for your reference.

 

 

 

Drinking Nitrate-Rich Beetroot Juice May Improve NO Levels in PAH Patients, Small Trial Shows

Drinking nitrate-rich beetroot juice can improve the production of nitric oxide in patients with pulmonary arterial hypertension (PAH), a small clinical trial shows.

Data from the trial was reported in the study, “Effects of oral supplementation with nitrate-rich beetroot juice in patients with pulmonary arterial hypertension — results from BEET-PAH an exploratory randomized, double-blind, placebo-controlled crossover study,” published in the Journal of Cardiac Failure.

Long-term Benefits of Ralinepag for PAH Patients Shown in Interim Data from Phase 2 Extension Trial

Long-term use of ralinepag, an investigational therapy being developed by Arena Pharmaceuticals, can promote positive changes in the outcome of patients with pulmonary arterial hypertension (PAH), interim data from a Phase 2 extension trial shows. After taking oral ralinepag for a median of up to 1.8 years, patients continued to show significant improvements in their exercise capacity and blood flow in the lung arteries, compared with before the start of treatment.

“We are pleased with the long-term safety, tolerability and efficacy that ralinepag has demonstrated in the open-label extension of our Phase 2 trial,” Preston Klassen, MD, Arena’s executive vice president of research and development and chief medical officer, said in a press release. “This is the first time an oral prostacyclin has shown durable, long-term improvements on hemodynamic and functional measures.”

Macitentan Tolerated in Portopulmonary Hypertension

In patients with portopulmonary hypertension (PoPH), pulmonary arterial hypertension (PAH) associated with portal hypertension, data from the OPsumit Users (OPUS) Registry (ClinicalTrials.gov Identifier: NCT02126943) suggest that the endothelin receptor antagonist macitentan can be used to target the endothelin pathway. Research was presented at the 2018 CHEST Annual Meeting, held October 6 through October 10 in San Antonio, Texas.

Ofev, Sildenafil Combo Shows No Added Benefit in IPF Patients with Poor Lung Function, Study Shows

Combining Ofev (nintedanib, marketed by Boehringer Ingelheim) with sildenafil does not offer additional clinical benefits when compared to Ofev treatment alone regarding quality of life and lung function in patients with idiopathic pulmonary fibrosis (IPF) and a very poor lung function, a Phase 3 study demonstrates.

The study, “Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis,” was published in the The New England Journal of Medicine.

A Potential Role for Exosomal Translationally Controlled Tumor Protein Export in Vascular Remodeling in Pulmonary Arterial Hypertension

Abstract: Pulmonary arterial hypertension (PAH) is characterized by increased proliferation and resistance to apoptosis of pulmonary vascular cells. Increased expression of translationally controlled tumor protein (TCTP), a prosurvival and antiapoptotic mediator, has recently been demonstrated in patients with heritable PAH; however, its role in the pathobiology of PAH remains unclear. Silencing of TCTP in blood outgrowth endothelial cells (BOECs) isolated from control subjects led to significant changes in morphology, cytoskeletal organization, increased apoptosis, and decreased directionality during migration. Because TCTP is also localized in extracellular vesicles, we isolated BOEC-derived extracellular vesicles (exosomes and microparticles) by sequential ultracentrifugation. BOECs isolated from patients harboring BMPR2 mutations released more exosomes than those derived from control subjects in proapoptotic conditions. Furthermore, TCTP expression was significantly higher in exosomes than in microparticles, indicating that TCTP is mainly exported via exosomes. Coculture assays demonstrated that exosomes transferred TCTP from ECs to pulmonary artery smooth muscle cells, suggesting a role for endothelial-derived TCTP in conferring proliferation and apoptotic resistance. In an experimental model of PAH, rats treated with monocrotaline demonstrated increased concentrations of TCTP in the lung and plasma. Consistent with this finding, we observed increased circulating TCTP levels in patients with idiopathic PAH compared with control subjects. Therefore, our data suggest an important role for TCTP in regulating the critical vascular cell phenotypes that have been implicated in the pathobiology of PAH. In addition, this research implicates TCTP as a potential biomarker for the onset and development of PAH.


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