FK506‐binding protein 51 plays a role in pulmonary endothelial cell phenotype switching

Abstract

It is well‐established that endothelial cells exhibit heterogeneity. Indeed, in the pulmonary vasculature, pulmonary artery endothelial cells (PAECs) and pulmonary microvascular endothelial cells (PMVECs) exhibit a many differences, including differences in proliferation rate and growth inhibition. PMVECs have a greater proliferative potential than PAECS and do not exhibit contact inhibition of growth in culture. Additionally, PMVECs express higher levels of FK506‐binding protein 51 (FKBP51) than PAECs, a trait that confers resistance to the store‐operated calcium current, Isoc. Here, we asked whether FKBP51 affects endothelial cell phenotype. Pulmonary arterial hypertension is marked by endothelial dysfunction and vascular remodeling, and it has been suggested that phenotype switching via endothelial‐to‐mesenchymal transition or resident stem cells may contribute to disease progression. We investigated the role of FKBP51 in phenotype switching using an FKPB51‐overexpressing PAEC cell line. FKBP51‐overexpressing PAECs showed a two‐fold increase in doubling time compared to wild type PAECs. PAECs grow in islands, exhibiting a cobblestone appearance and contact‐dependent growth inhibition. On the other hand, FKBP51‐overexpressing PAECs have a PMVEC‐like phenotype, wherein cells take on a spindle‐like morphology when sub‐confluent and are not growth inhibited at confluence. In addition, FKBP51‐overexpressing PAECs show increased smooth muscle actin, an indicator of endothelial cell dedifferentiation, as compared to wild‐type PAECs. Taken together, these data suggest that FKBP51 may play an important role in phenotype switching in PAECs.Support or Funding InformationAmerican Heart Association #17AIREA33680155This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.