Extracellular adenosine enhances pulmonary artery vasa vasorum endothelium cell barrier function via the Gi/ELMO1/Rac1/PKA-dependent signaling mechanisms.

In this study we investigated in more detail the mechanisms linking Gi activation to downstream barrier protection pathways. Using a small interference RNA (siRNA) technique and Transendothelial Electrical Resistance (TER) assay, we found that the adaptor protein, ELMO1, the tyrosine phosphatase Shp2, and atypical Gi- and Rac-mediated PKA activation are implicated in VVEC barrier enhancement. In contrast, the actin-interacting GTP-binding protein, girdin and the PAK1 downstream target, LIM kinase, are not involved in this response. In addition, adenosine-dependent cytoskeletal rearrangement involves activation of cofilin and inactivation of ERM regulatory cytoskeletal proteins, consistent with a barrier-protective mechanism. Collectively, our data indicate that targeting adenosine receptors and downstream barrier protective pathways in VVEC may represent novel pharmacologic approach for hypoxia-induced VV hyper permeability in PH and possibly other cardiovascular diseases associated with impaired vascular barrier function. PMID: 32432925 [PubMed - as supplied by publisher]
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research