PMID- 25209241
OWN - NLM
STAT- MEDLINE
DCOM- 20151109
LR  - 20211021
IS  - 1466-609X (Electronic)
IS  - 1364-8535 (Print)
IS  - 1364-8535 (Linking)
VI  - 18
IP  - 5
DP  - 2014 Sep 11
TI  - Enhanced monocyte chemoattractant protein-1 production in aging mice exaggerates 
      cardiac depression during endotoxemia.
PG  - 527
LID - 10.1186/s13054-014-0527-8 [doi]
LID - 527
AB  - INTRODUCTION: Endotoxemia and the systemic inflammatory response syndrome have a 
      significant impact on post-surgery outcome, particularly in the elderly. The 
      cytokine response to endotoxin is altered by aging. We tested the hypothesis that 
      vulnerability to endotoxemic cardiac depression increases with aging due to 
      age-related augmentation of myocardial inflammatory responses. METHODS: Adult (4 
      to 6 months) and old (20 to 22 months) C57/BL6 mice were treated with endotoxin 
      (0.5 mg/kg, iv). Left ventricle (LV) function was assessed using a microcatheter 
      system. Chemokines and cytokines in plasma and myocardium were analyzed by 
      enzyme-linked immunosorbent assay (ELISA). Mononuclear cells in the myocardium 
      were examined using immunofluorescence staining. RESULTS: Old mice displayed 
      worse LV function (cardiac output: 3.0 +/- 0.2 mL/min versus 4.4 +/- 0.3 mL/min in 
      adult mice) following endotoxin treatment. The exaggerated cardiac depression in 
      old mice was associated with higher levels of monocyte chemoattractant protein-1 
      (MCP-1) and keratinocyte chemoattractant (KC) in plasma and myocardium, greater 
      myocardial accumulation of mononuclear cells, and greater levels of tumor 
      necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta) and interleukin 6 (IL-6) in 
      plasma and myocardium. Neutralization of MCP-1 resulted in greater reductions in 
      myocardial mononuclear cell accumulation and cytokine production, and greater 
      improvement in LV function in old mice while neutralization of KC had a minimal 
      effect on LV function. CONCLUSION: Old mice have enhanced inflammatory responses 
      to endotoxemia that lead to exaggerated cardiac functional depression. MCP-1 
      promotes myocardial mononuclear cell accumulation and cardiodepressant cytokines 
      production, and plays an important role in the endotoxemic cardiomyopathy in old 
      mice. The findings suggest that special attention is needed to protect the heart 
      in the elderly with endotoxemia.
FAU - Slimani, Hanan
AU  - Slimani H
FAU - Zhai, Yufeng
AU  - Zhai Y
FAU - Yousif, Nasser G
AU  - Yousif NG
FAU - Ao, Lihua
AU  - Ao L
FAU - Zeng, Qingchun
AU  - Zeng Q
FAU - Fullerton, David A
AU  - Fullerton DA
FAU - Meng, Xianzhong
AU  - Meng X
LA  - eng
GR  - R01 AG039545/AG/NIA NIH HHS/United States
GR  - AG039545/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140911
PL  - England
TA  - Crit Care
JT  - Critical care (London, England)
JID - 9801902
RN  - 0 (Biomarkers)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
SB  - IM
CIN - Crit Care. 2014;18(6):638. PMID: 25672938
MH  - Aging/physiology
MH  - Animals
MH  - Biomarkers/blood
MH  - Chemokine CCL2/antagonists & inhibitors/*biosynthesis/blood/immunology
MH  - Cytokines/blood
MH  - Endotoxemia/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardium/*metabolism
MH  - Ventricular Dysfunction, Left
PMC - PMC4172828
EDAT- 2014/09/12 06:00
MHDA- 2015/11/10 06:00
PMCR- 2014/09/11
CRDT- 2014/09/12 06:00
PHST- 2014/05/27 00:00 [received]
PHST- 2014/09/02 00:00 [accepted]
PHST- 2014/09/12 06:00 [entrez]
PHST- 2014/09/12 06:00 [pubmed]
PHST- 2015/11/10 06:00 [medline]
PHST- 2014/09/11 00:00 [pmc-release]
AID - s13054-014-0527-8 [pii]
AID - 527 [pii]
AID - 10.1186/s13054-014-0527-8 [doi]
PST - epublish
SO  - Crit Care. 2014 Sep 11;18(5):527. doi: 10.1186/s13054-014-0527-8.