RRC ID 27775
Author Zong J, Salim M, Zhou H, Bian ZY, Dai J, Yuan Y, Deng W, Zhang JY, Zhang R, Wu QQ, Tang QZ.
Title NOD2 deletion promotes cardiac hypertrophy and fibrosis induced by pressure overload.
Journal Lab. Invest.
Abstract Nucleotide-binding oligomerization domain-2 (NOD2, also designated CARD15), a member of the NOD-leucine-rich repeat (LRR) protein family (also called the CATERPILLAR family), is upregulated in atheroma lesions and has an important role in regulating the intracellular recognition of bacterial components by immune cells. However, the effect of NOD2 on cardiac hypertrophy induced by a pathological stimulus has not been determined. Here, we investigated the effects of NOD2 deficiency on cardiac hypertrophy induced by aortic banding (AB) in mice. Cardiac hypertrophy was evaluated by echocardiographic, hemodynamic, pathological, and molecular analyses. NOD2 expression was upregulated in cardiomyocytes after aortic banding surgery in wild-type (WT) mice. NOD2 deficiency promoted cardiac hypertrophy and fibrosis 4 weeks after AB. Further, the enhanced activation of TLR4 and the MAPKs, NF-κB and TGF-β/Smad pathways were found in NOD2-knockout (KO) mice compared with WT mice. Our results suggest that NOD2 attenuates cardiac hypertrophy and fibrosis via regulation of multiple pathways.
Volume 93(10)
Pages 1128-36
Published 2013-10
DOI 10.1038/labinvest.2013.99
PII labinvest201399
PMID 23958879
MeSH Animals Cardiomegaly / etiology Cardiomegaly / metabolism* Cardiomegaly / pathology Cardiomegaly / physiopathology Cell Nucleus Disease Models, Animal* Disease Progression Fibrosis Hypertension / physiopathology* MAP Kinase Signaling System Male Mice Mice, Inbred C57BL Mice, Knockout Myocardium / metabolism* Myocardium / pathology Nod2 Signaling Adaptor Protein / biosynthesis Nod2 Signaling Adaptor Protein / genetics Nod2 Signaling Adaptor Protein / metabolism* Phosphorylation Protein Processing, Post-Translational Protein Transport Random Allocation Smad Proteins / metabolism Toll-Like Receptor 4 / metabolism Transcription Factor RelA / metabolism Up-Regulation
IF 3.684
Times Cited 9
Mice Card15 KO(RBRC01869)