PMID- 22140485
OWN - NLM
STAT- MEDLINE
DCOM- 20120409
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 11
DP  - 2011
TI  - Alterations in the interleukin-1/interleukin-1 receptor antagonist balance 
      modulate cardiac remodeling following myocardial infarction in the mouse.
PG  - e27923
LID - 10.1371/journal.pone.0027923 [doi]
LID - e27923
AB  - BACKGROUND: Healing after acute myocardial infarction (AMI) is characterized by 
      an intense inflammatory response and increased Interleukin-1 (IL-1) tissue 
      activity. Genetically engineered mice lacking the IL-1 receptor (IL-1R1-/-, not 
      responsive to IL-1) or the IL-1 receptor antagonist (IL-1Ra, enhanced response to 
      IL-1) have an altered IL-1/IL-1Ra balance that we hypothesize modulates infarct 
      healing and cardiac remodeling after AMI. METHODS: IL-1R1-/- and IL-1Ra-/- male 
      mice and their correspondent wild-types (WT) were subjected to permanent coronary 
      artery ligation or sham surgery. Infarct size (trichrome scar size), apoptotic 
      cell death (TUNEL) and left ventricular (LV) dimensions and function 
      (echocardiography) were measured prior to and 7 days after surgery. RESULTS: When 
      compared with the corresponding WT, IL-1R1-/- mice had significantly smaller 
      infarcts (-25%), less cardiomyocyte apoptosis (-50%), and reduced LV enlargement 
      (LV end-diastolic diameter increase [LVEDD], -20%) and dysfunction (LV ejection 
      fraction [LVEF] decrease, -50%), whereas IL-1Ra-/- mice had significantly larger 
      infarcts (+75%), more apoptosis (5-fold increase), and more severe LV enlargement 
      (LVEDD increase,+30%) and dysfunction (LVEF decrease, +70%)(all P values <0.05). 
      CONCLUSIONS: An imbalance in IL-1/IL-1Ra signaling at the IL-1R1 level modulates 
      the severity of cardiac remodeling after AMI in the mouse, with reduced IL-1R1 
      signaling providing protection and unopposed IL-1R1 signaling providing harm.
FAU - Abbate, Antonio
AU  - Abbate A
AD  - Victoria Johnson Research Laboratory and VCU Pauley Heart Center, Virginia 
      Commonwealth University, Richmond, Virginia, United States of America. 
      aabbate@mcvh-vcu.edu
FAU - Salloum, Fadi N
AU  - Salloum FN
FAU - Van Tassell, Benjamin W
AU  - Van Tassell BW
FAU - Vecile, Elena
AU  - Vecile E
FAU - Toldo, Stefano
AU  - Toldo S
FAU - Seropian, Ignacio
AU  - Seropian I
FAU - Mezzaroma, Eleonora
AU  - Mezzaroma E
FAU - Dobrina, Aldo
AU  - Dobrina A
LA  - eng
GR  - KL2 RR031989/RR/NCRR NIH HHS/United States
GR  - KL2 TR000057/TR/NCATS NIH HHS/United States
GR  - UL1 TR000058/TR/NCATS NIH HHS/United States
GR  - KL2RR031989-01/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111128
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Heart Ventricles/metabolism/pathology
MH  - Interleukin 1 Receptor Antagonist Protein/deficiency/*metabolism
MH  - Interleukin-1/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardial Infarction/*metabolism/*physiopathology/surgery
MH  - Myocardium/*metabolism/*pathology
MH  - Myocytes, Cardiac/metabolism/pathology
MH  - Survival Analysis
MH  - Systole
MH  - Ventricular Remodeling/*physiology
PMC - PMC3225370
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/12/06 06:00
MHDA- 2012/04/10 06:00
PMCR- 2011/11/28
CRDT- 2011/12/06 06:00
PHST- 2011/06/30 00:00 [received]
PHST- 2011/10/27 00:00 [accepted]
PHST- 2011/12/06 06:00 [entrez]
PHST- 2011/12/06 06:00 [pubmed]
PHST- 2012/04/10 06:00 [medline]
PHST- 2011/11/28 00:00 [pmc-release]
AID - PONE-D-11-12260 [pii]
AID - 10.1371/journal.pone.0027923 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(11):e27923. doi: 10.1371/journal.pone.0027923. Epub 2011 Nov 28.