title: Identification of gene signatures regulated by carvedilol in mouse heart.
abstract: Chronic treatment with the β-blocker carvedilol has been shown to reduce established maladaptive left ventricle (LV) hypertrophy and to improve LV function in experimental heart failure. However, the detailed mechanisms by which carvedilol improves LV failure are incompletely understood. We previously showed that carvedilol is a β-arrestin-biased β1-adrenergic receptor ligand, which activates cellular pathways in the heart independent of G protein-mediated second messenger signaling. More recently, we have demonstrated by microRNA (miR) microarray analysis that carvedilol upregulates a subset of mature and pre-mature miRs, but not their primary miR transcripts in mouse hearts. Here, we next sought to identify the effects of carvedilol on LV gene expression on a genome-wide basis. Adult mice were treated with carvedilol or vehicle for 1 wk. RNA was isolated from LV tissue and hybridized for microarray analysis. Gene expression profiling analysis revealed a small group of genes differentially expressed after carvedilol treatment. Further analysis categorized these genes into pathways involved in tight junction, malaria, viral myocarditis, glycosaminoglycan biosynthesis, and arrhythmogenic right ventricular cardiomyopathy. Genes encoding proteins in the tight junction, malaria, and viral myocarditis pathways were upregulated in the LV by carvedilol, while genes encoding proteins in the glycosaminoglycan biosynthesis and arrhythmogenic right ventricular cardiomyopathy pathways were downregulated by carvedilol. These gene expression changes may reflect the molecular mechanisms that underlie the functional benefits of carvedilol therapy.
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
authors.forename: Jian-Peng
authors.initials: JP
authors.lastname: Teoh
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
authors.forename: Kyoung-Mi
authors.initials: KM
authors.lastname: Park
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Broskova
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
authors.forename: Felix R
authors.initials: FR
authors.lastname: Jimenez
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Bayoumi
authors.affiliation: Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; and.
authors.forename: Krystal
authors.initials: K
authors.lastname: Archer
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
authors.forename: Huabo
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
authors.forename: John
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; and.
authors.forename: Neal L
authors.initials: NL
authors.lastname: Weintraub
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; and.
authors.forename: Yaoliang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia ilkim@gru.edu.
authors.forename: Il-Man
authors.initials: IM
authors.lastname: Kim
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000235:genetics; D000077261:Carvedilol; D005786:Gene Expression Regulation / Q000187:drug effects*; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000235:genetics; D006352:Heart Ventricles / Q000187:drug effects*; D008288:Malaria / Q000235:genetics; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000235:genetics; D011412:Propanolamines / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D006025:Glycosaminoglycans; D011412:Propanolamines; D011506:Proteins; D000077261:Carvedilol
keywords: beta-blocker; biased G protein-coupled receptor signaling; gene regulation; left ventricle; transcriptome