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Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice.

Publication ,  Journal Article
Rau, CD; Romay, MC; Tuteryan, M; Wang, JJ-C; Santolini, M; Ren, S; Karma, A; Weiss, JN; Wang, Y; Lusis, AJ
Published in: Cell Syst
January 25, 2017

We previously reported a genetic analysis of heart failure traits in a population of inbred mouse strains treated with isoproterenol to mimic catecholamine-driven cardiac hypertrophy. Here, we apply a co-expression network algorithm, wMICA, to perform a systems-level analysis of left ventricular transcriptomes from these mice. We describe the features of the overall network but focus on a module identified in treated hearts that is strongly related to cardiac hypertrophy and pathological remodeling. Using the causal modeling algorithm NEO, we identified the gene Adamts2 as a putative regulator of this module and validated the predictive value of NEO using small interfering RNA-mediated knockdown in neonatal rat ventricular myocytes. Adamts2 silencing regulated the expression of the genes residing within the module and impaired isoproterenol-induced cellular hypertrophy. Our results provide a view of higher order interactions in heart failure with potential for diagnostic and therapeutic insights.

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Published In

Cell Syst

DOI

ISSN

2405-4712

Publication Date

January 25, 2017

Volume

4

Issue

1

Start / End Page

121 / 128.e4

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Systems Biology
  • Signal Transduction
  • Myocytes, Cardiac
  • Myocardium
  • Mice, Inbred Strains
  • Mice
  • Isoproterenol
  • Heart Ventricles
  • Heart Failure
 

Citation

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Rau, C. D., Romay, M. C., Tuteryan, M., Wang, J.-C., Santolini, M., Ren, S., … Lusis, A. J. (2017). Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice. Cell Syst, 4(1), 121-128.e4. https://doi.org/10.1016/j.cels.2016.10.016
Rau, Christoph D., Milagros C. Romay, Mary Tuteryan, Jessica J-C Wang, Marc Santolini, Shuxun Ren, Alain Karma, James N. Weiss, Yibin Wang, and Aldons J. Lusis. “Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice.Cell Syst 4, no. 1 (January 25, 2017): 121-128.e4. https://doi.org/10.1016/j.cels.2016.10.016.
Rau CD, Romay MC, Tuteryan M, Wang JJ-C, Santolini M, Ren S, et al. Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice. Cell Syst. 2017 Jan 25;4(1):121-128.e4.
Rau, Christoph D., et al. “Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice.Cell Syst, vol. 4, no. 1, Jan. 2017, pp. 121-128.e4. Pubmed, doi:10.1016/j.cels.2016.10.016.
Rau CD, Romay MC, Tuteryan M, Wang JJ-C, Santolini M, Ren S, Karma A, Weiss JN, Wang Y, Lusis AJ. Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice. Cell Syst. 2017 Jan 25;4(1):121-128.e4.
Journal cover image

Published In

Cell Syst

DOI

ISSN

2405-4712

Publication Date

January 25, 2017

Volume

4

Issue

1

Start / End Page

121 / 128.e4

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Systems Biology
  • Signal Transduction
  • Myocytes, Cardiac
  • Myocardium
  • Mice, Inbred Strains
  • Mice
  • Isoproterenol
  • Heart Ventricles
  • Heart Failure