TY - JOUR
T1 - Depletion of cardiac 14-3-3η protein adversely influences pathologic cardiac remodeling during myocardial infarction after coronary artery ligation in mice
AU - Sreedhar, Remya
AU - Arumugam, Somasundaram
AU - Thandavarayan, Rajarajan A
AU - Giridharan, Vijayasree V
AU - Karuppagounder, Vengadeshprabhu
AU - Pitchaimani, Vigneshwaran
AU - Afrin, Rejina
AU - Harima, Meilei
AU - Nakamura, Masahiko
AU - Suzuki, Kenji
AU - Gurusamy, Narasimman
AU - Krishnamurthy, Prasanna
AU - Watanabe, Kenichi
N1 - Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - BACKGROUND/OBJECTIVES: 14-3-3η protein, a dimeric phosphoserine-binding protein, provides protection against adverse cardiac remodeling during pressure-overload induced heart failure in mice. To identify its role in myocardial infarction (MI), we have used mice with cardio-specific expression of dominant-negative 14-3-3η protein mutant (DN14-3-3) and performed the surgical ligation of left anterior descending coronary artery.METHODS: We have performed echocardiography to assess cardiac function, protein expression analysis using Western blotting, mRNA expression by real time-reverse transcription polymerase chain reaction and histopathological analyses.RESULTS: DN14-3-3 mice with MI displayed reduced survival, left ventricular ejection fraction and fractional shortening. Interestingly, DN14-3-3 mice subjected to MI showed increased cardiac hypertrophy, inflammation, fibrosis and apoptosis as compared to their wild-type counterparts. Mechanistically, DN14-3-3 mice with MI exhibited activation of endoplasmic reticulum (ER) stress and markers of maladaptive cardiac remodeling. Cardiac regeneration marker expression also decreased drastically in the DN14-3-3 mice with MI.CONCLUSION: Depletion of the 14-3-3η protein causes cardiac dysfunction and reduces survival in mice with MI, probably via exacerbation of ER stress and death signaling pathways and suppression of cardiac regeneration. Thus, identification of drugs that can modulate cardiac 14-3-3η protein levels may probably provide a novel protective therapy for heart failure.
AB - BACKGROUND/OBJECTIVES: 14-3-3η protein, a dimeric phosphoserine-binding protein, provides protection against adverse cardiac remodeling during pressure-overload induced heart failure in mice. To identify its role in myocardial infarction (MI), we have used mice with cardio-specific expression of dominant-negative 14-3-3η protein mutant (DN14-3-3) and performed the surgical ligation of left anterior descending coronary artery.METHODS: We have performed echocardiography to assess cardiac function, protein expression analysis using Western blotting, mRNA expression by real time-reverse transcription polymerase chain reaction and histopathological analyses.RESULTS: DN14-3-3 mice with MI displayed reduced survival, left ventricular ejection fraction and fractional shortening. Interestingly, DN14-3-3 mice subjected to MI showed increased cardiac hypertrophy, inflammation, fibrosis and apoptosis as compared to their wild-type counterparts. Mechanistically, DN14-3-3 mice with MI exhibited activation of endoplasmic reticulum (ER) stress and markers of maladaptive cardiac remodeling. Cardiac regeneration marker expression also decreased drastically in the DN14-3-3 mice with MI.CONCLUSION: Depletion of the 14-3-3η protein causes cardiac dysfunction and reduces survival in mice with MI, probably via exacerbation of ER stress and death signaling pathways and suppression of cardiac regeneration. Thus, identification of drugs that can modulate cardiac 14-3-3η protein levels may probably provide a novel protective therapy for heart failure.
U2 - 10.1016/j.ijcard.2015.08.142
DO - 10.1016/j.ijcard.2015.08.142
M3 - Article
C2 - 26386943
SN - 0167-5273
VL - 202
SP - 146
EP - 153
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -