title: NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice.
abstract: Pulmonary hypertension occurs with prolonged exposure to chronic hypoxia in both adults and neonates. The Ca(2+)-dependent transcription factor, nuclear factor of activated T cells isoform c3 (NFATc3), has been implicated in chronic hypoxia-induced pulmonary arterial remodeling in adult mice. Therefore, we hypothesized that NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice. The aim of this study was to determine whether 1) NFATc3 mediates chronic hypoxia-induced increases in right ventricular systolic pressure in adult mice; 2) NFATc3 is activated in neonatal mice exposed to chronic hypoxia; and 3) NFATc3 is involved in chronic hypoxia-induced right ventricular hypertrophy and pulmonary vascular remodeling in neonatal mice. Adult mice were exposed to hypobaric hypoxia for 2, 7, and 21 days. Neonatal mouse pups were exposed for 7 days to hypobaric chronic hypoxia within 2 days after delivery. Hypoxia-induced increases in right ventricular systolic pressure were absent in NFATc3 knockout adult mice. In neonatal mice, chronic hypoxia caused NFAT activation in whole lung and nuclear accumulation of NFATc3 in both pulmonary vascular smooth muscle and endothelial cells. In addition, heterozygous NFATc3 neonates showed less right ventricular hypertrophy and pulmonary artery wall thickness in response to chronic hypoxia than did wild-type neonates. Our results suggest that NFATc3 mediates pulmonary hypertension and vascular remodeling in both adult and neonatal mice.
authors: Department of Pediatrics, School of Medicine, University of New Mexico, Albuquerque, 87131, USA.
authors: R
authors: R
authors: Bierer
authors: C H
authors: CH
authors: Nitta
authors: J
authors: J
authors: Friedman
authors: S
authors: S
authors: Codianni
authors: S
authors: S
authors: de Frutos
authors: J A
authors: JA
authors: Dominguez-Bautista
authors: T A
authors: TA
authors: Howard
authors: T C
authors: TC
authors: Resta
authors: L V Gonzalez
authors: LV
authors: Bosc
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D055786:Gene Knockout Techniques; D017930:Genes, Reporter; D006579:Heterozygote; D006976:Hypertension, Pulmonary / Q000150:complications / Q000378:metabolism*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000378:metabolism; D000860:Hypoxia; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology*
chemical_list: D050778:NFATC Transcription Factors; C494009:Nfatc3 protein, mouse; D008156:Luciferases