title: NOD2 deletion promotes cardiac hypertrophy and fibrosis induced by pressure overload.
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.
authors: 1] Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China [2] Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China.
authors: Jing
authors: J
authors: Zong
authors: Mohamed
authors: M
authors: Salim
authors: Heng
authors: H
authors: Zhou
authors: Zhou-yan
authors: ZY
authors: Bian
authors: Jia
authors: J
authors: Dai
authors: Yuan
authors: Y
authors: Yuan
authors: Wei
authors: W
authors: Deng
authors: Jie-yu
authors: JY
authors: Zhang
authors: Rui
authors: R
authors: Zhang
authors: Qing-qing
authors: QQ
authors: Wu
authors: Qi-zhu
authors: QZ
authors: Tang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002467:Cell Nucleus; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D006973:Hypertension / Q000503:physiopathology*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011897:Random Allocation; D051785:Smad Proteins / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C498144:Rela protein, mouse; D051785:Smad Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA