Cheng-Jun Hu, Aya Laux, Aneta Gandjeva, Liyi Wang, Min Li, Dale Brown, Suzette Riddle, Vitaly O Kheyfets, Rubin M Tuder, Hui Zhang, Kurt R Stenmark
Hypoxia-inducible factor (HIF) has received much attention as a potential pulmonary hypertension (PH) treatment target because inhibition of HIF reduces the severity of established PH in rodent models. However, the limitations of small animal models of PH in predicting the therapeutic effects of pharmacologic interventions in human PH are well known. Therefore, we sought to interrogate the role of HIFs in driving the activated phenotype of PH cells from human and bovine vessels. We first established that pulmonary arteries (PAs) from human and bovine PH lungs exhibit markedly increased expression of direct HIF target genes (CA9, GLUT1, and NDRG1), as well as of cytokines/chemokines (CCL2, CSF2, CXCL12, and IL6), growth factors (FGF1, FGF2, PDGFb, and TGFA), and apoptosis resistance genes (BCL2, BCL2L1, and BIRC5)...
March 21, 2023: American Journal of Respiratory Cell and Molecular Biology