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PLoS One. 2012;7(6):e39997. doi: 10.1371/journal.pone.0039997. Epub 2012 Jun 29.

An analysis of the myocardial transcriptome in a mouse model of cardiac dysfunction with decreased cholinergic neurotransmission.

Author information

1
Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Abstract

Autonomic dysfunction is observed in many cardiovascular diseases and contributes to cardiac remodeling and heart disease. We previously reported that a decrease in the expression levels of the vesicular acetylcholine transporter (VAChT) in genetically-modified homozygous mice (VAChT KD(HOM)) leads to decreased cholinergic tone, autonomic imbalance and a phenotype resembling cardiac dysfunction. In order to further understand the molecular changes resulting from chronic long-term decrease in parasympathetic tone, we undertook a transcriptome-based, microarray-driven approach to analyze gene expression changes in ventricular tissue from VAChT KD(HOM) mice. We demonstrate that a decrease in cholinergic tone is associated with alterations in gene expression in mutant hearts, which might contribute to increased ROS levels observed in these cardiomyocytes. In contrast, in another model of cardiac remodeling and autonomic imbalance, induced through chronic isoproterenol treatment to increase sympathetic drive, these genes did not appear to be altered in a pattern similar to that observed in VAChT KD(HOM) hearts. These data suggest the importance of maintaining a fine balance between the two branches of the autonomic nervous system and the significance of absolute levels of cholinergic tone in proper cardiac function.

PMID:
22768193
PMCID:
PMC3386908
DOI:
10.1371/journal.pone.0039997
[Indexed for MEDLINE]
Free PMC Article

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