Novel Protective Role of Myeloid Differentiation 1 in Pathological Cardiac Remodelling.
Myeloid differentiation 1 (MD-1), a secreted protein interacting with radioprotective 105 (RP105), plays an important role in Toll-like receptor 4 (TLR4) signalling pathway. Previous studies showed that MD-1 may be restricted in the immune system. In this study, we demonstrated for the first time that MD-1 was highly expressed in both human and animal hearts. We also discovered that cardiac-specific overexpression of MD-1 significantly attenuated pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of MD-1 had the opposite effects. Similar results were observed for in vitro angiotensin II-induced neonatal rat cardiomyocyte hypertrophy. The antihypertrophic effects of MD-1 under hypertrophic stimuli were associated with the blockage of MEK-ERK 1/2 and NF-κB signalling. Blocking MEK-ERK 1/2 signalling with a pharmacological inhibitor (U0126) greatly attenuated the detrimental effects observed in MD-1 knockout cardiomyocytes exposed to angiotensin II stimuli. Similar results were observed by blocking NF-κB signalling with a pharmacological inhibitor (BAY11-7082). Our data indicate that MD-1 inhibits cardiac hypertrophy and suppresses cardiac dysfunction during the remodelling process, which is dependent on its modulation of the MEK-ERK 1/2 and NF-κB signalling pathways. Thus, MD-1 might be a novel target for the treatment of pathological cardiac hypertrophy.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Xiaojv
X
Xiong
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Yu
Y
Liu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Yang
Y
Mei
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Jianye
J
Peng
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Zhiqiang
Z
Wang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Bin
B
Kong
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Peng
P
Zhong
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Liang
L
Xiong
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Dajun
D
Quan
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Qi
Q
Li
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Guangji
G
Wang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.|Cardiovascular Research Institute of Wuhan University, Wuhan, Hubei Province, PR China.|Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
He
H
Huang
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics* / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D020257:Ventricular Remodeling
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000954:Antigens, Surface; C113553:Ly86 protein, mouse; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; D000804:Angiotensin II; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3