PMID- 26747780
OWN - NLM
STAT- MEDLINE
DCOM- 20160727
LR  - 20200930
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 310
IP  - 6
DP  - 2016 Mar 15
TI  - Genetic ablation of interleukin-18 does not attenuate hypobaric hypoxia-induced 
      right ventricular hypertrophy.
PG  - L542-50
LID - 10.1152/ajplung.00166.2015 [doi]
AB  - Interleukin-18 (IL-18), a proinflammatory cytokine, has been implicated in 
      pathologic left ventricular hypertrophy and is elevated in plasma of heart 
      failure patients. However, IL-18 blockade strategies have been conflicting. The 
      purpose of these experiments was to determine whether genetic ablation of IL-18 
      would protect mice against hypobaric hypoxia (HH)-induced right ventricular (RV) 
      hypertrophy, a condition in which chamber-specific inflammation is prominent. We 
      hypothesized that IL-18 knockout (KO) mice would be protected while wild-type 
      (WT) mice would demonstrate RV hypertrophy in response to HH exposure. KO and WT 
      mice were exposed to HH for 7 wk, and control mice were exposed to normoxic 
      ambient air. Following echocardiography, the RV was dissected and flash-frozen 
      for biochemical analyses. HH exposure increased IL-18 mRNA (P = 0.08) in RV from 
      WT mice. Genetic ablation of IL-18 mildly attenuated RV hypertrophy as assessed 
      by myocyte size. However, IL-18 KO mice were not protected against HH-induced 
      organ-level remodeling, as evidenced by higher RV weights, elevated RV systolic 
      pressure, and increased RV anterior wall thickness compared with normoxic KO 
      mice. These RV changes were similar to those seen in HH-exposed WT mice. 
      Compensatory upregulation of other proinflammatory cytokines IL-2 and stromal 
      cell-derived factor-1 was seen in the HH-KO animals, suggesting that activation 
      of parallel inflammatory pathways might mitigate the effect of IL-18 KO. These 
      data suggest targeted blockade of IL-18 alone is not a viable therapeutic 
      strategy in this model.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Bruns, Danielle R
AU  - Bruns DR
AD  - Department of Medicine, Cardiology, University of Colorado-Denver, Aurora, 
      Colorado.
FAU - Buttrick, Peter M
AU  - Buttrick PM
AD  - Department of Medicine, Cardiology, University of Colorado-Denver, Aurora, 
      Colorado.
FAU - Walker, Lori A
AU  - Walker LA
AD  - Department of Medicine, Cardiology, University of Colorado-Denver, Aurora, 
      Colorado Lori.walker@ucdenver.edu.
LA  - eng
GR  - 2T32-HL-007822-16/HL/NHLBI NIH HHS/United States
GR  - P01-HL014985-36A1/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160108
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (Interleukin-18)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Chemokine CXCL12/genetics/metabolism
MH  - Collagen/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Gene Expression
MH  - Hypertension, Pulmonary/etiology/genetics/metabolism
MH  - Hypertrophy, Right Ventricular/etiology/*genetics/metabolism
MH  - Hypoxia/*complications/genetics/metabolism
MH  - Interleukin-18/*genetics/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocardium/metabolism/pathology
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational
MH  - Ventricular Remodeling
PMC - PMC4796262
OTO - NOTNLM
OT  - IL-18
OT  - cardiac
OT  - pulmonary hypertension
OT  - right ventricle
EDAT- 2016/01/10 06:00
MHDA- 2016/07/28 06:00
PMCR- 2017/03/15
CRDT- 2016/01/10 06:00
PHST- 2015/05/28 00:00 [received]
PHST- 2015/12/29 00:00 [accepted]
PHST- 2016/01/10 06:00 [entrez]
PHST- 2016/01/10 06:00 [pubmed]
PHST- 2016/07/28 06:00 [medline]
PHST- 2017/03/15 00:00 [pmc-release]
AID - ajplung.00166.2015 [pii]
AID - L-00166-2015 [pii]
AID - 10.1152/ajplung.00166.2015 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2016 Mar 15;310(6):L542-50. doi: 
      10.1152/ajplung.00166.2015. Epub 2016 Jan 8.