Commensal microbiota contributes to chronic endocarditis and arrhythmia in TAX1BP1 deficient mice.

ABSTRACT: Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules with its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mouse develops age-dependent inflammatory constitution in multiple organs including heart, liver, skin and succumb to premature heart failure. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed that the 588 transcription alterations. SAA3 (serum amyloid A3), at 1,180-fold induction (FI), CHI3L1(361-FI), HP(187-FI), IL1B(122-FI) and SPP1/OPN(101-FI) and WIF1 (Wnt inhibitory factor 1) at 11-fold decrease implied extensive inflammation and tissue degeneration at this microenvironment. Intense Saa3 staining and significant reduction of I-κBα at the same area, massive infiltration of inflammatory lymphocytes and edema formation at the peripheral areas of sinoatrial and atrioventricular node were also observed and electrocardiogram indicated atrioventricular conduction defect (elongated PQ-interval) in TAX1BP1-KO mice. Since antibiotics-induced ‘germ free’ status for three months significantly ameliorated these chronic autoimmune and altered cardiac excitation properties, we conclude that these chronic pathological conditions, as we named ‘pseudo-infective endocarditis’ were boosted by the commensal microbiota those who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation and cardiac dysfunction.

ORGANISM(S): Mus musculus

PROVIDER: GSE43932 | GEO | 2014/02/01

SECONDARY ACCESSION(S): PRJNA188554

REPOSITORIES: GEO