Epoprostenol sodium for treatment of pulmonary arterial hypertension

Abstract

The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required.

Cefminox, a Dual Agonist of Prostacyclin Receptor and Peroxisome Proliferator-Activated Receptor-Gamma Identified by Virtual Screening, Has Therapeutic Efficacy against Hypoxia-Induced Pulmonary Hypertension in Rats

“…Prostacyclin (also known as prostaglandin I 2 ) is produced in vascular endothelial cells and acts via the prostacyclin receptor (IP) of pulmonary artery smooth muscle cells (PASMCs) to cause vasodilation and inhibit PASMC proliferation (LeVarge, 2015 ). Prostacyclin production and IP expression are reduced in PAH (Saito et al, 2015 ), and analogs of prostacyclin are recommended as a pharmacotherapeutic option for patients with PAH in WHO Functional Class III/IV (Galie et al, 2016 ). The selective IP agonist oral selexipag has also displayed therapeutic effects, with acceptable tolerability in patients with PAH (Del Pozo et al, 2017 ; Honorato Pérez, 2017 ).…”

Effect of miR-23a on anoxia-induced phenotypic transformation of smooth muscle cells of rat pulmonary arteries and regulatory mechanism

“…Previous studies often focused on the mechanism of changes in related bioactive molecules involved in regulating functions such as proliferation, apoptosis and migration (7–9). Results obtained from other studies revealed that anoxia can significantly downregulate the expression of PASMC contractile phenotype marker proteins (10,11). However, the specific mechanism of this downregulation is still unclear.…”

Circulating Apoptotic Signals During Acute and Chronic Exposure to High Altitude in Kyrgyz Population

“…In the case of TRAIL and FasL, we have shown a noticeable increase in the gene expression for both targets during the hypoxic exposure of PASMCs, as compared to their respective normoxic controls. Limited evidences from the literature implicated these two signals in the context of pulmonary vascular disease (Hameed et al, 2012; Saito et al, 2015). Interestingly, although TRAIL is usually considered as pro-apoptotic mediator, its role in experimental PH pathogenesis has been described (Hameed et al, 2012).…”