title: Depletion of cardiac 14-3-3η protein adversely influences pathologic cardiac remodeling during myocardial infarction after coronary artery ligation in mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors.forename: Remya
authors.initials: R
authors.lastname: Sreedhar
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors.forename: Somasundaram
authors.initials: S
authors.lastname: Arumugam
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan; Department of Cardiovascular Sciences, Houston Methodist Research Center, Houston 77087, TX, USA.
authors.forename: Rajarajan A
authors.initials: RA
authors.lastname: Thandavarayan
authors.affiliation: J.K.K. Nattraja College of Pharmacy, Natarajapuram, Komarapalayam 638183, Namakkal District, Tamil Nadu, India.
authors.forename: Vijayasree V
authors.initials: VV
authors.lastname: Giridharan
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors.forename: Vengadeshprabhu
authors.initials: V
authors.lastname: Karuppagounder
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors.forename: Vigneshwaran
authors.initials: V
authors.lastname: Pitchaimani
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors.forename: Rejina
authors.initials: R
authors.lastname: Afrin
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors.forename: Meilei
authors.initials: M
authors.lastname: Harima
authors.affiliation: Department of Cardiology, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi 400 8506, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951 8510, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
authors.forename: Narasimman
authors.initials: N
authors.lastname: Gurusamy
authors.affiliation: Department of Cardiovascular Sciences, Houston Methodist Research Center, Houston 77087, TX, USA.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Krishnamurthy
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan. Electronic address: somasundaram143@gmail.com.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D048948:14-3-3 Proteins / Q000096:biosynthesis / Q000172:deficiency*; D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D006801:Humans; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D048948:14-3-3 Proteins
keywords: 14-3-3η protein; Apoptosis; Echocardiography; Endoplasmic reticulum stress; Ischemia; Myocardial infarction