Cardiac inflammation in genetic dilated cardiomyopathy caused by MYBPC3 mutation

J Mol Cell Cardiol. 2017 Jan;102:83-93. doi: 10.1016/j.yjmcc.2016.12.002. Epub 2016 Dec 10.


Cardiomyopathies are a leading cause of heart failure and are often caused by mutations in sarcomeric genes, resulting in contractile dysfunction and cellular damage. This may stimulate the production of a robust proinflammatory response. To determine whether myocardial inflammation is associated with cardiac dysfunction in dilated cardiomyopathy (DCM) caused by MYBPC3 mutation, we used the well-characterized cMyBP-C(t/t) mouse model of DCM at 3months of age. Compared to wild type (WT) mice, DCM mice exhibited significantly decreased fractional shortening (36.4±2% vs. 15.5±1.0%, p<0.0001) and significantly increased spleen weight (5.3±0.3 vs. 7.2±0.4mg/mm, p=0.002). Intriguingly, flow cytometry analysis revealed a significant increase in total (CD45+CD11b+Ly6C-MHCII+F480+) macrophages (6.5±1.4% vs. 14.8±1.4%, p=0.002) and classically activated (CD45+CD11b+Ly6C-MHCII+F480+CD206-) proinflammatory (M1) macrophages (3.4±0.8% vs. 10.3±1.2%, p=0.0009) in DCM hearts as compared with WT hearts. These results were further confirmed by immunofluorescence analysis of heart tissue sections. Splenic red pulp (CD11b+Ly6C+MHCIIlowF480hi) macrophages were significantly elevated (1.3±0.1% vs. 2.4±0.1%, p=0.0001) in DCM compared to WT animals. Serum cytokine analysis in DCM animals exhibited a significant increase (0.65±0.2 vs. 2.175±0.5pg/mL, p=0.02) in interleukin (IL)-6 compared to WT animals. Furthermore, RNA-seq analysis revealed the upregulation of inflammatory pathways in the DCM hearts. Together, these data indicate a robust proinflammatory response in DCM hearts, likely in response to cellular damage triggered by MYBPC3 mutation and resultant contractile dysfunction.

Keywords: Dilated cardiomyopathy; Inflammation; MYBPC3; Mouse models; Sarcomere biology.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Cardiomyopathy, Dilated / complications*
  • Cardiomyopathy, Dilated / diagnosis
  • Cardiomyopathy, Dilated / genetics*
  • Carrier Proteins / genetics*
  • Cluster Analysis
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Genetic Predisposition to Disease
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Transgenic
  • Mutation*
  • Myocardial Contraction
  • Myocarditis / etiology*
  • Myocarditis / metabolism
  • Splenomegaly
  • Ventricular Dysfunction


  • Biomarkers
  • Carrier Proteins
  • myosin-binding protein C