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Evidence of endothelial‐to‐mesenchymal transition in an animal model of pulmonary arterial hypertension
Author(s) -
Morrow K. Adam,
Brown Jonathan R.,
Morrow Rebekah L.,
Snyder Emily A.,
Vasauskas Audrey A
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb579
Subject(s) - vascular remodelling in the embryo , bmpr2 , pulmonary artery , pulmonary hypertension , endothelial stem cell , endothelium , hypoxia (environmental) , right ventricular hypertrophy , endothelial dysfunction , medicine , biology , endocrinology , pathology , chemistry , bone morphogenetic protein , biochemistry , organic chemistry , oxygen , in vitro , gene
Pulmonary arterial hypertension (PAH), a disease of the small pulmonary arteries, is characterized by pulmonary vasoconstriction, vascular cell proliferation, and vascular remodeling leading to right ventricular hypertrophy and failure. The remodeled vessels exhibit signs of endothelial layer damage and smooth muscle cell proliferation. It is also well‐established that mutations in the bone morphogenetic protein receptor 2 (BMPR2) predispose individuals to development of PAH. Recent studies in PAH mouse models and in cultured human pulmonary artery endothelial cells (where BMPR2 has been experimentally knocked down) suggest that endothelial cells involved in the vascular remodeling of PAH undergo transdifferentiation. Here, we show that pulmonary artery endothelial cells (PAECs) isolated from the rat Sugen (SU516)/hypoxia model of pulmonary arterial hypertension exhibit phenotypic changes characteristic of endothelial‐to‐mesenchymal transition (EndMT). Preliminary data also suggest decreased BMPR2 expression in the PAH model PAECs. Cells were obtained from the University of South Alabama Center for Lung Biology (CLB). Briefly, Fisher 344 rats were injected with SU5416 (20mg/kg) or vehicle control and exposed to hypoxia (10% O 2 or normoxia for control animals) for three weeks and returned to normoxia for at least two weeks. PAECs were harvested using established CLB protocol. PAECs from the PAH animals (SURAT) exhibited a significant increase in alpha smooth muscle actin (αSMA) expression as compared to the control PAECs, as evidenced by immunocytochemistry and real time PCR. These cells retained expression of endothelial cell markers von Willebrand Factor (vWF) and platelet endothelial cell adhesion molecule (PECAM‐1). However, expression of both PECAM‐1 and vWF was decreased in the SURAT cells compared to control PAECs. Expression of tight junctional protein‐1, vascular adhesion molecule‐1 (VCAM‐1), intracellular adhesion molecule‐1 (ICAM‐1), claudin‐1, and selectin was also decreased in the SURAT PAECs as compared to control cells. These data suggest that PAECS exhibit signs of cellular reprogramming in Sugen/hypoxia‐treated animals, and also provide insight into a cellular model that directly correlates with a well‐established animal model of PAH. Support or Funding Information Supported by NIH1R15HL137135‐01A1 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .