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Experimental Investigation of Profibrotic Cell Signaling in Pulmonary Arterial Adventitial Fibroblasts
Author(s) -
Wang Ariel,
Valdez-Jasso Daniela
Publication year - 2020
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.2020.34.s1.07341
Subject(s) - myofibroblast , extracellular matrix , fibronectin , elastin , fibroblast , fibrosis , vascular remodelling in the embryo , pulmonary artery , pulmonary fibrosis , microbiology and biotechnology , lung , neointima , pathology , chemistry , biology , medicine , in vitro , biochemistry , restenosis , stent
Pulmonary arterial adventitial fibroblasts (PAAFs) are important regulators of fibrotic vascular remodeling during pulmonary arterial hypertension (PAH). PAAFs can be activated into myofibroblasts that produce more extracellular matrix (ECM), which contributes significantly to pulmonary vascular remodeling and stiffening in disease progression. There are currently no therapies that reverse the matrix remodeling and vascular stiffening that occurs during PAH. In order to better identify treatments to target adventitial fibrosis, we sought to investigate the interplay between major pathways that have been reported to regulate myofibroblast transformation and ECM expression in PAAFs. Compared with other fibroblast types, there is a scarcity of experimental data on mechano‐signaling in PAAFs, therefore more in vitro experiments are needed to determine which pathways are crucial to creating a systems biology model that describes mechanosignaling in PAAFs. We have developed techniques to decellularize and reseed pulmonary arteries from Sprague‐Dawley rats to investigate the effects that purely the ECM have on the phenotypic transition of PAAFs. We surmise that pulmonary artery ECM alone from rats with PAH will have a significant impact on the transition of PAAFs into myofibroblasts and will investigate this difference using quantitative RT‐PCR. We will measure collagen I, collagen III expression, and alpha smooth muscle actin to measure the level of myofibroblast transition. In addition, levels of matrix proteins such as elastin and fibronectin will be measured via histology to characterize the level of fibrosis. Combining these results with a profibrotic signaling network model, we can use these methods to identify potential combinatorial therapeutics to prevent or inhibit wall remodeling to treat PAH. Support or Funding Information This work was partially funded by the American Heart Association Scientist Development Grant 16SDG29670010, and the National Institutes of Health NHLBI 1 T32 HL105373 and NHLBI 1 R01 HL137100.