Muscle Ring Finger-1 regulation of right-sided heart transcriptional responses to hypoxia in vivo.. Mus musculus

To determine the role of cardiomyocyte muscle ring finger-1 (MuRF1) in vivo, we employed whole genome microarray expression profiling as a discovery platform to identify genes differentially regulated by MuRF1 using MuRF1-/- and alphaMHC (cardiomyocyte-specific) MuRF1 transgenic mice in a model of pulmonary hypertension-induced right sided heart failure. Mice were placed in hypoxia chambers set at 10.0% oxygen (partial pressure of oxygen roughly 65 mmHg in Albuquerque) and monitored both by the digital feedback control system (Biospherix, Colorado) as well as by a secondary O2/CO2 monitor (O2Cap, OxiGraf, Inc.; Mountain View, CA). The hypoxia exposure lasted 3 weeks with twice-weekly cage changes and standard 12 h light:dark cycle. Multiple genes from the microarray expression profile were quantified in the same RNA samples by real-time PCR to confirm their expression. Overall design: Hypoxia-induced pulmonary hypertension and right heart failure was induced over 3 weeks of mice being placed in a hypoxia chamber with 10.0% oxygen (partial pressure of oxygen approximately 65 mm Hg in Albequerque, NM). Three biological replicates of each condition (hypoxia) and genotype were used from independent experiments.