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Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.

Publication ,  Journal Article
Wang, JJ-C; Rau, C; Avetisyan, R; Ren, S; Romay, MC; Stolin, G; Gong, KW; Wang, Y; Lusis, AJ
Published in: PLoS Genet
July 2016

We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls.

Duke Scholars

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Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

July 2016

Volume

12

Issue

7

Start / End Page

e1006038

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Quantitative Trait Loci
  • Natriuretic Peptide, Brain
  • Myosin Type II
  • Myosin Heavy Chains
  • Myocardium
  • Mice
  • Isoproterenol
  • Hypertrophy, Left Ventricular
  • Humans
 

Citation

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Wang, J.-C., Rau, C., Avetisyan, R., Ren, S., Romay, M. C., Stolin, G., … Lusis, A. J. (2016). Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model. PLoS Genet, 12(7), e1006038. https://doi.org/10.1371/journal.pgen.1006038
Wang, Jessica Jen-Chu, Christoph Rau, Rozeta Avetisyan, Shuxun Ren, Milagros C. Romay, Gabriel Stolin, Ke Wei Gong, Yibin Wang, and Aldons J. Lusis. “Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.PLoS Genet 12, no. 7 (July 2016): e1006038. https://doi.org/10.1371/journal.pgen.1006038.
Wang JJ-C, Rau C, Avetisyan R, Ren S, Romay MC, Stolin G, et al. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model. PLoS Genet. 2016 Jul;12(7):e1006038.
Wang, Jessica Jen-Chu, et al. “Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.PLoS Genet, vol. 12, no. 7, July 2016, p. e1006038. Pubmed, doi:10.1371/journal.pgen.1006038.
Wang JJ-C, Rau C, Avetisyan R, Ren S, Romay MC, Stolin G, Gong KW, Wang Y, Lusis AJ. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model. PLoS Genet. 2016 Jul;12(7):e1006038.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

July 2016

Volume

12

Issue

7

Start / End Page

e1006038

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Quantitative Trait Loci
  • Natriuretic Peptide, Brain
  • Myosin Type II
  • Myosin Heavy Chains
  • Myocardium
  • Mice
  • Isoproterenol
  • Hypertrophy, Left Ventricular
  • Humans