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Endothelium‐targeted deletion of Nox4 attenuates hypoxia‐induced increases in right ventricular pressure (1089.19)
Author(s) -
Sutliff Roy,
Kleinhenz Jennifer,
Ma Jing,
Hart C.
Publication year - 2014
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.28.1_supplement.1089.19
Subject(s) - nox4 , right ventricular hypertrophy , pulmonary hypertension , hypoxia (environmental) , nadph oxidase , medicine , pulmonary artery , ventricular pressure , endocrinology , biology , chemistry , cardiology , oxygen , blood pressure , oxidative stress , organic chemistry
The complex pathobiology of pulmonary hypertension (PH) involves reactive oxygen species (ROS) and increased pulmonary vascular resistance. NADPH oxidase 4 (Nox4) has been shown to be an important source of ROS in PH, and systemic administration of a Nox4 pharmacological inhibitor attenuated hypoxia‐induced PH. To further explore the role of pulmonary vascular Nox4 in hypoxia‐induced PH, a floxed Nox4 mouse model was crossed with mice that: 1) express Cre recombinase driven by the tie‐2 promoter to target deletion of endothelial Nox4 (eNox4), or 2) express Cre recombinase driven by the smooth muscle myosin heavy chain promoter to target deletion of smooth muscle Nox4 (smNox4). Littermate controls, eNox4 and smNox4 mice were exposed to normoxia (21% O 2 ) or hypoxia (10% O 2 ) for 3 weeks. PH development was assessed by measuring right ventricular systolic pressures (RVSP) and right ventricular hypertrophy (RVH). Hypoxia‐induced increases in RVSP were attenuated in the eNox4 model (N=5; p<0.05) whereas the RVSP in smNox4 knockout mice was not different than controls. In contrast, hypoxia‐induced RVH was no different than controls in either the eNox4 or smNox4 mice. These studies suggest that endothelial Nox4 promotes pulmonary vascular derangements involved in PH pathogenesis. Grant Funding Source : Supported by VA Merit Review 1I01BX001910 (CMH) and NIH grant R01 HL102167 (CMH and RLS).