August 2024 PVRI Community Call with Steven D. Nathan, Alexander Seidinger and Daniela Wenzel

In this PH Community Call we discussed: 

• Risk Assessment Models and Event-Free Survival in Pulmonary Arterial Hypertension
• PINK1/Parkin Deficiency Enhances Vascular Remodeling and Aggravates Hypoxia-induced Pulmonary Hypertension

My journey into studying nitric oxide (NO) bioavailability developed as I explored the role of nitrite ions. The traditional view that nitrite was merely an inactive byproduct of NO oxidation was a perspective I sought to challenge. As I continued my research at Papworth and Addenbrooke's Hospitals under Professor Higenbottam, I hypothesized that nitrite ions could be a source of NO bioactivity.

Phenotypic transition of pulmonary artery smooth muscle cells (PASMCs) under hypoxic conditions, which in turn causes increased proliferation and migration capacity, is an important pathological process in Hypoxic pulmonary hypertension (HPH). Although research on the phenotypic transition of PASMCs has been ongoing, little is known about the specific molecular mechanisms underlying this process.

Activin-A is elevated in pulmonary arterial hypertension (PAH) patients, and reportedly suppresses BMPR-II. This suggests one mechanism of action for PAH drug, sotatercept, an activin-ligand trap. However, we were unable to confirm that activin-A reduces BMPR-II in pulmonary endothelial cells. Thus, it seems unlikely that sotatercept influences BMPR-II or PAH via this mechanism.