title: Activating transcription factor 3 deficiency promotes cardiac hypertrophy, dysfunction, and fibrosis induced by pressure overload.
abstract: Activating transcription factor 3 (ATF3), which is encoded by an adaptive-response gene induced by various stimuli, plays an important role in the cardiovascular system. However, the effect of ATF3 on cardiac hypertrophy induced by a pathological stimulus has not been determined. Here, we investigated the effects of ATF3 deficiency on cardiac hypertrophy using in vitro and in vivo models. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements and by pathological and molecular analysis. ATF3 deficiency promoted cardiac hypertrophy, dysfunction and fibrosis after 4 weeks of AB compared to the wild type (WT) mice. Furthermore, enhanced activation of the MEK-ERK1/2 and JNK pathways was found in ATF3-knockout (KO) mice compared to WT mice. In vitro studies performed in cultured neonatal mouse cardiomyocytes confirmed that ATF3 deficiency promotes cardiomyocyte hypertrophy induced by angiotensin II, which was associated with the amplification of MEK-ERK1/2 and JNK signaling. Our results suggested that ATF3 plays a crucial role in the development of cardiac hypertrophy via negative regulation of the MEK-ERK1/2 and JNK pathways.
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Heng
authors: H
authors: Zhou
authors: Di-Fei
authors: DF
authors: Shen
authors: Zhou-Yan
authors: ZY
authors: Bian
authors: Jing
authors: J
authors: Zong
authors: Wei
authors: W
authors: Deng
authors: Yan
authors: Y
authors: Zhang
authors: Yuan-Yuan
authors: YY
authors: Guo
authors: Hongliang
authors: H
authors: Li
authors: Qi-Zhu
authors: QZ
authors: Tang
mesh_terms: D051700:Activating Transcription Factor 3 / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis; D006439:Hemodynamics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D017725:Ventricular Pressure
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases