title: Loss of TRADD attenuates pressure overload-induced cardiac hypertrophy through regulating TAK1/P38 MAPK signalling in mice.
abstract: We investigated the role of tumour necrosis factor receptor (TNFR)-associated death domain (TRADD) on pressure overload-induced cardiac hypertrophy and the underlying molecular mechanisms by using a TRADD deficiency mice model. 6-8 weeks wild-type and TRADD knockout mice were performed to transverse aorta constriction (TAC) or sham operation (6-8 mice for each group). 14 days after TAC, cardiac function was measured by echocardiography, as well as by pathological and molecular analyses of heart samples. The expressions of cardiac hypertrophic and fibrotic markers were detected by qPCR. Phosphorylated and total TAK1, Akt, and p38 MAPK levels were examined by Western blotting. The ratios of lung or heart/body weight, wall thickness/chamber diameter of left ventricular and cross area of cardiomyocyte were significantly reduced in TRADD knockout (KO) mice than those of wild-type mice after TAC. Moreover, cardiac hypertrophic and fibrotic markers were downregulated in TRADD knockout mice than those of wild-type mice following TAC. Protein expression analysis showed phosphorylated TAK1, p38 MAPK and AKT were upregulated after TAC in both wild-type and TRADD KO mice, phosphorylation of TAK1 and p38 MAPK was reduced more remarkably after TRADD deficiency, while phosphorylated AKT expression was similar between TRADD KO and wild-type mice following TAC. Our data suggest that TRADD KO blunts pressure overload-induced cardiac hypertrophy through mediating TAK1/p38 MAPK but not AKT phosphorylation in mice.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Suzhou Medical University, 188 Shizi Road, Suzhou, Jiangsu, 215006, China; Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University & Yuying Children Hospital, 109 Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
authors.forename: Lianpin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Cardiology, No 411 Hospital of People's Liberation Army, 15 East Jiangwan Road, Shanghai, 200081, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Laparoscopic Surgery, The First Hospital Affiliated to Wenzhou Medical College, Wenzhou, Zhejiang, 325027, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Oral Prophylaxis and Hygiene, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University & Yuying Children Hospital, 109 Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
authors.forename: Qike
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University & Yuying Children Hospital, 109 Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University & Yuying Children Hospital, 109 Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
authors.forename: Jiafeng
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University & Yuying Children Hospital, 109 Xueyuan Road, Wenzhou, Zhejiang, 325027, China.
authors.forename: Maoping
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University & Yuying Children Hospital, 109 Xueyuan Road, Wenzhou, Zhejiang, 325027, China. Electronic address: lileiii@yahoo.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Suzhou Medical University, 188 Shizi Road, Suzhou, Jiangsu, 215006, China. Electronic address: th.reestonee@gmail.com.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053199:TNF Receptor-Associated Death Domain Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D020930:MAP Kinase Kinase Kinases; D051057:Proto-Oncogene Proteins c-akt; D053199:TNF Receptor-Associated Death Domain Protein; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7; C481226:Tradd protein, mouse
keywords: Cardiac hypertrophy; Pressure overload; TAK1; TRADD