TRAF3IP2 mediates aldosterone/salt-induced cardiac hypertrophy and fibrosis

Siva S.V.P. Sakamuri, Anthony J. Valente, Jalahalli M. Siddesha, Patrice Delafontaine, Ulrich Siebenlist, Jason D. Gardner, Chandrasekar Bysani

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Aberrant activation of the renin-angiotensin-aldosterone system (RAAS) contributes to adverse cardiac remodeling and eventual failure. Here we investigated whether TRAF3 Interacting Protein 2 (TRAF3IP2), a redox-sensitive cytoplasmic adaptor molecule and an upstream regulator of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), mediates aldosterone-induced cardiac hypertrophy and fibrosis. Wild type (WT) and TRAF3IP2-null mice were infused with aldosterone (0.2 mg/kg/day) for 4 weeks along with 1%NaCl in drinking water. Aldosterone/salt, but not salt alone, upregulated TRAF3IP2 expression in WT mouse hearts. Further, aldosterone elevated blood pressure to a similar extent in both WT and TRAF3IP2-null groups. However, TRAF3IP2 gene deletion attenuated aldosterone/salt-induced (i) p65 and c-Jun activation, (ii) extracellular matrix (collagen Iα1 and collagen IIIα1), matrix metalloproteinase (MMP2), lysyl oxidase (LOX), inflammatory cytokine (IL-6 and IL-18), chemokine (CXCL1 and CXCL2), and adhesion molecule (ICAM1) mRNA expression in hearts, (iii) IL-6, IL-18, and MMP2 protein levels, (iv) systemic IL-6 and IL-18 levels, and (iv) cardiac hypertrophy and fibrosis. These results indicate that TRAF3IP2 is a critical signaling intermediate in aldosterone/salt-induced myocardial hypertrophy and fibrosis, and thus a potential therapeutic target in hypertensive heart disease.

Original languageEnglish (US)
Pages (from-to)84-92
Number of pages9
JournalMolecular and Cellular Endocrinology
StatePublished - Jul 5 2016


  • Act1
  • Aldosterone
  • CIKS
  • Cardiac fibrosis
  • Cardiac hypertrophy
  • RAAS
  • TRAF3IP2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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