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Oxidative deregulation of ferrochelatase mediates transferrin receptor‐induced remodeling in pulmonary arterial smooth muscle cells in monocrotaline‐induced pulmonary arterial hypertension
Author(s) -
Alhawaj Raed,
Ghadhanfar Elham,
Cherian Susan
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.550.8
Subject(s) - ferrochelatase , hemin , chemistry , transferrin receptor , heme , reactive oxygen species , hypoxia (environmental) , vascular smooth muscle , bosentan , medicine , endocrinology , receptor , pharmacology , endothelin receptor , biochemistry , enzyme , oxygen , organic chemistry , smooth muscle
Pulmonary arterial hypertension (PAH) is driven by pulmonary arterial smooth muscle cell (PASMC) vasoconstriction and remodeling. One of the many drivers of PAH‐PASMCs remodeling is increased transferrin receptor‐1 (TFR‐1) expression. Under pro‐PAH conditions, PASMCs exhibit elevated reactive oxygen species (ROS) production which may disrupt ferrochelatase normal heme production. We evaluated the role played by ROS‐deregulated ferrochelatase in TFR‐1‐mediated PAH‐PASMCs remodeling. Intra‐lobar pulmonary arteries (PA) isolated from monocrotaline‐induced PAH model in Sprague‐Dawley rats have shown an up‐regulation of ferrochelatase expression, that can be a result of hypoxia‐inducible factor (HIF) mediated up‐regulation to compensate for decreased ferrochelatase catalytic activity. Decreased ferrochelatase activity was evident in the decreased levels of hemin (oxidized form of heme) in isolated PAH‐PAs. Endothelin‐1 (ET‐1), which is an inducer of mitochondrial ROS and is one of the mediators of PAH; was used in a 24‐hour organ culture of isolated endothelium‐removed bovine pulmonary arteries (BPA). ET‐1 cultured BPAs have shown decreased hemin levels and increased TFR‐1 expression. Thus, ROS‐deregulated ferrochelatase may promote vascular remodeling in PAH through the impairment of hemin‐mediated downregulation of TFR‐1 receptors in PASMCs. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .