p90 ribosomal S6 kinase 3 contributes to cardiac insufficiency in α-tropomyosin Glu180Gly transgenic mice

Catherine L. Passariello, Marjorie Gayanilo, Michael D. Kritzer, Hrishikesh Thakur, Zoharit Cozacov, Francesca Rusconi, David Wieczorek, Michael Sanders, Jinliang Li, Michael S. Kapiloff

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Myocardial interstitial fibrosis is an important contributor to the development of heart failure. Type 3 p90 ribosomal S6 kinase (RSK3) was recently shown to be required for concentric myocyte hypertrophy under in vivo pathological conditions. However, the role of RSK family members in myocardial fibrosis remains uninvestigated. Transgenic expression of α-tropomyosin containing a Glu180Gly mutation (TM180) in mice of a mixed C57BL/6:FVB/N background induces a cardiomyopathy characterized by a small left ventricle, interstitial fibrosis, and diminished systolic and diastolic function. Using this mouse model, we now show that RSK3 is required for the induction of interstitial fibrosis in vivo. TM180 transgenic mice were crossed to RSK3 constitutive knockout (RSK3-/-) mice. Although RSK3 knockout did not affect myocyte growth, the decreased cardiac function and mild pulmonary edema associated with the TM180 transgene were attenuated by RSK3 knockout. The improved cardiac function was consistent with reduced interstitial fibrosis in the TM180;RSK3-/- mice as shown by histology and gene expression analysis, including the decreased expression of collagens. The specific inhibition of RSK3 should be considered as a potential novel therapeutic strategy for improving cardiac function and the prevention of sudden cardiac death in diseases in which interstitial fibrosis contributes to the development of heart failure.

Original languageEnglish (US)
Pages (from-to)H1010-H1019
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume305
Issue number7
DOIs
StatePublished - Oct 1 2013

Keywords

  • α-tropomyosin
  • Fibrosis
  • Ribosomal S6 kinase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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    Passariello, C. L., Gayanilo, M., Kritzer, M. D., Thakur, H., Cozacov, Z., Rusconi, F., Wieczorek, D., Sanders, M., Li, J., & Kapiloff, M. S. (2013). p90 ribosomal S6 kinase 3 contributes to cardiac insufficiency in α-tropomyosin Glu180Gly transgenic mice. American Journal of Physiology - Heart and Circulatory Physiology, 305(7), H1010-H1019. https://doi.org/10.1152/ajpheart.00237.2013