TRIF promotes angiotensin II-induced cross-talk between fibroblasts and macrophages in atrial fibrosis

Biochem Biophys Res Commun. 2015 Aug 14;464(1):100-5. doi: 10.1016/j.bbrc.2015.05.131. Epub 2015 Jun 5.

Abstract

Aims: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear.

Methods and results: We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages.

Conclusions: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis.

Keywords: Atrial fibroblasts; Atrial fibrosis; Macrophages; TRIF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / antagonists & inhibitors
  • Adaptor Proteins, Vesicular Transport / genetics*
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Angiotensin II / metabolism
  • Angiotensin II / pharmacology
  • Animals
  • Atrial Fibrillation / genetics
  • Atrial Fibrillation / metabolism*
  • Atrial Fibrillation / pathology
  • Atrial Fibrillation / surgery
  • Cell Communication
  • Cell Proliferation / drug effects
  • Chemotaxis
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibrosis
  • Gene Expression Regulation
  • Heart Atria / metabolism*
  • Heart Atria / pathology
  • Heart Atria / surgery
  • Humans
  • Losartan / pharmacology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction

Substances

  • Adaptor Proteins, Vesicular Transport
  • RNA, Small Interfering
  • TICAM1 protein, human
  • Angiotensin II
  • Losartan