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: Jian-Peng Teoh, Kyoung-Mi Park, Zuzana Broskova, Felix R Jimenez, Ahmed S Bayoumi, Krystal Archer, Huabo Su, John Johnson, Neal L Weintraub, Yaoliang Tang, Il-Man Kim
• Journal: Physiological genomics (Physiol Genomics) Vol. 47 Issue 9 Pg. 376-85 (Sep 2015) ISSN: 1531-2267 [Electronic] United States
• PMID: 26152686 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Adrenergic beta-Antagonists
• Carbazoles
• Glycosaminoglycans
• Propanolamines
• Proteins
• Carvedilol

Topics

• Adrenergic beta-Antagonists (pharmacology)
• Animals
• Carbazoles (pharmacology)
• Cardiomyopathies (genetics)
• Carvedilol
• Gene Expression Regulation (drug effects)
• Glycosaminoglycans (biosynthesis, genetics)
• Heart Ventricles (drug effects)
• Malaria (genetics)
• Mice, Inbred C57BL
• Myocarditis (genetics)
• Propanolamines (pharmacology)
• Proteins (genetics, metabolism)
• Ventricular Function, Left (drug effects)