Introducing Historical Vignettes in Pulmonary Circulation

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. 

Pulmonary hypertension (PH) constitutes a critical challenge in cardiopulmonary medicine with a pathogenesis that is multifaceted and intricate. Ion channels, crucial determinants of cellular electrochemical gradient modulation, have emerged as significant participants in the pathophysiological progression of PH. 

Female sex increases risk of Group I pulmonary arterial hypertension by roughly threefold, but the mechanism is unclear. Low expression of Cyp1b1, an enzyme that metabolizes estrogens, is associated with disease penetrance, particularly in women. We previously found that lower Pparγ levels in murine PAH models, which may drive disease, are rescued by estrogen blockade.

Pulmonary vascular disease is not a single condition; rather it can accompany a variety of pathologies that impact the pulmonary vasculature. Applying precision medicine strategies to better phenotype, diagnose, monitor, and treat pulmonary vascular disease is increasingly possible with the growing accessibility of powerful clinical and research tools.