Depletion of cardiac 14-3-3η protein adversely influences pathologic cardiac remodeling during myocardial infarction after coronary artery ligation in mice

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• 作者：Remya Sreedhar^a ; Somasundaram Arumugam^a ; Rajarajan A. Thandavarayan^a ; ^b ; Vijayasree V. Giridharan^c ; Vengadeshprabhu Karuppagounder^a ; Vigneshwaran Pitchaimani^a ; Rejina Afrin^a ; Meilei Harima^a ; Masahiko Nakamura^d ; Kenji Suzuki^e ; Narasimman Gurusamy^f ; Prasanna Krishnamurthy^b ; Kenichi Watanabe^a ; ^{somasundaram143@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：14-3-3η protein ; Myocardial infarction ; Ischemia ; Apoptosis ; Echocardiography ; Endoplasmic reticulum stress
• 刊名：International Journal of Cardiology
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：202
• 期：Complete
• 页码：146-153
• 全文大小：1176 K

文摘

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.