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Hypoxia Stimulates Pulmonary Artery Endothelial Proliferation via 5‐Lipoxygenase
Author(s) -
Porter Kristi Michelle,
Sutliff Roy L
Publication year - 2012
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.26.1_supplement.1129.18
Subject(s) - zileuton , hypoxic pulmonary vasoconstriction , hypoxia (environmental) , cell growth , chemistry , western blot , pulmonary hypertension , vasoconstriction , endothelial stem cell , arachidonate 5 lipoxygenase , pharmacology , medicine , endocrinology , biology , biochemistry , enzyme , in vitro , oxygen , arachidonic acid , organic chemistry , gene
Pulmonary Hypertension (PH) is a progressive disorder characterized by endothelial dysfunction and proliferation. Hypoxia induces PH by increasing vascular remodeling. A potential mediator in hypoxia‐induced PH development is 5‐Lipoxygenase (ALOX5). While ALOX5 metabolites have been shown to promote pulmonary vasoconstriction and endothelial cell proliferation, the contribution of ALOX5 to hypoxia‐induced proliferation remains unknown. We hypothesize that hypoxia exposure stimulates HPAEC proliferation by increasing ALOX5 expression and activity. Human pulmonary artery endothelial cells (HPAEC) were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions for 24‐, 48‐, or 72 hours. In a subset of cells, the ALOX5 inhibitor, zileuton, was administered during hypoxia exposure. Cells were then harvested to assess ALOX5 expression via qRT‐PCR and western blot. HPAEC proliferation was assessed using an MTT assay and PCNA Western analysis. Our studies demonstrate that 24‐ and 48 hours of hypoxia exposure have no effect on HPAEC proliferation or ALOX5 expression. Seventy two hours of hypoxia significantly increases HPAEC ALOX5 expression and HPAEC proliferation. Zileuton administration attenuates hypoxia‐induced HPAEC proliferation. These studies indicate that hypoxia exposure induces HPAEC proliferation by activating the ALOX5 pathway.