Mas1 Receptor Activation is Necessary and Sufficient to Transduce ACE2 Effect in PAH, But Ang(1-7) Alone is Insufficient

Pulmonary arterial endothelial and smooth muscle cell homeostasis is regulated through the bone morphogenetic protein (BMP) and transforming growth factor beta (TGF-β) receptor pathways. Pathway imbalance results in pulmonary hypertension (PH). Each pathway has ligands and modulators influencing this balance. How these pathways differ in pediatric PH patients is unknown.

Pulmonary arterial hypertension (PAH) is characterized by progressive narrowing and obliteration of distal, pre-capillary pulmonary vessels. Yet, noninvasive biomarkers that reflect this disease-defining process are lacking. A systematic review of PAH studies that measured circulating progenitor cells (CPCs) or circulating endothelial cells (CECs) in PAH by flow cytometry was performed to understand how future studies, leveraging state-of-the-art single-cell analyses, can advance the field.

The history of advances in understanding pulmonary circulation is long, dating to the 13th century. Subsequent centuries produced halting progress until the 20th century when investigators applied right heart catheterization and light-microscopy to better understand the physiology and pathology of pulmonary hypertension (PH). The work of Paul Wood, Cornelis Wagenvoort, and others during the first seven decades of the 20th century set the stage for five decades of extraordinary progress.

Transcription factor TBX4 rare variants associate with pulmonary arterial hypertension (PAH), particularly in children, and are the second most common cause of heritable PAH. However, TBX4's down-stream targets and the molecular and cellular pathways these targets regulate remain largely unknown in PAH.