Role of prostanoids, nitric oxide and endothelin pathways in pulmonary hypertension due to COPD

Abstract

Pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD) is classified as Group 3 PH, with no current proven targeted therapies. Studies suggest that cigarette smoke, the most risk factor for COPD can cause vascular remodelling and eventually PH as a result of dysfunction and proliferation of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs). In addition, hypoxia is a known driver of pulmonary vascular remodelling in COPD, and it is also thought that the presence of hypoxia in patients with COPD may further exaggerate cigarette smoke-induced vascular remodelling; however, the underlying cause is not fully understood. Three main pathways (prostanoids, nitric oxide and endothelin) are currently used as a therapeutic target for the treatment of patients with different groups of PH. However, drugs targeting these three pathways are not approved for patients with COPD-associated PH due to lack of evidence. Thus, this review aims to shed light on the role of impaired prostanoids, nitric oxide and endothelin pathways in cigarette smoke- and hypoxia-induced pulmonary vascular remodelling and also discusses the potential of using these pathways as therapeutic target for patients with PH secondary to COPD.

Therapeutic Targets and Precision Medicine in COPD: Inflammation, Ion Channels, Both, or Neither?

“…Among GPCRs, these include the receptors for adenosine (the A 2A , A 2B and A 3 receptors), which act through G-proteins to regulate adenylyl cyclase [129][130][131][132][133], and the prostanoid receptor, which acts through a different G-protein to regulate adenylyl cyclase 2 (Ref. [134]). Among members of other PDE families, PDE8 isoforms have been implicated in the regulation of airway smooth muscle tone [135,136] and may be promising therapeutic targets in the future.…”