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.
Subject(s)
Hypertension, Pulmonary/metabolism , NFATC Transcription Factors/metabolism , Pulmonary Artery/pathology , Analysis of Variance , Animals , Animals, Newborn , Apoptosis , Cell Nucleus/metabolism , Cell Proliferation , Gene Knockout Techniques , Genes, Reporter , Heterozygote , Hypertension, Pulmonary/complications , Hypertrophy, Right Ventricular/etiology , Hypertrophy, Right Ventricular/metabolism , Hypoxia , Luciferases/biosynthesis , Luciferases/genetics , Male , Mice , Mice, Inbred BALB C , Mice, Knockout , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/physiology , NFATC Transcription Factors/genetics , Protein Transport , Pulmonary Artery/metabolismABSTRACT
This study evaluated the efficacy of green lipped mussel (GLM), added to a complete dry diet, for alleviating clinical signs of arthritis in dogs. A double-blind longitudinal study design was used with 31 mixed-breed dogs exhibiting varying degrees of arthritis. Each dog was evaluated by a veterinarian and joints were individually scored for degree of pain, swelling, crepitus, and reduction in range of movement. Summation of all scores for an individual dog comprised its total arthritis score. At baseline, dogs were randomly allocated to control and test groups. Both groups were fed the same base dry diet, to which 0.3% GLM powder was added for dogs in the test group. The change in total arthritis score by the end of 6 weeks showed there was significant improvement (P < .05) in the test group versus the control group. Significant improvements were also observed in joint pain and swelling scores in the test group. Changes in joint crepitus and range of joint movement were not significantly different between the test and control groups. These findings provide strong evidence that GLM incorporated into a complete dry diet can help alleviate arthritis symptoms in dogs.
