PMID- 27513082
OWN - NLM
STAT- MEDLINE
DCOM- 20180220
LR  - 20181113
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 47
IP  - 1
DP  - 2017 Jan
TI  - The AMPK Activator Aicar Ameliorates Age-Dependent Myocardial Injury in Murine 
      Hemorrhagic Shock.
PG  - 70-78
AB  - The development of myocardial dysfunction in patients with hemorrhagic shock is 
      significantly impacted by the patient age. AMP-activated protein kinase (AMPK) is 
      a pivotal orchestrator of energy homeostasis, which coordinates metabolic 
      recovery after cellular stress. We investigated whether AMPK-regulated pathways 
      are age-dependent in hemorrhage-induced myocardial injury and whether AMPK 
      activation by 5-amino-4-imidazolecarboxamide riboside (AICAR) affords 
      cardioprotective effects. Anesthetized C57/BL6 young (3-5 months old) and mature 
      (9-12 months old) male mice were subjected to hemorrhagic shock by blood 
      withdrawing followed by resuscitation with shed blood and Lactated Ringer's 
      solution. Mice were sacrificed at 3 h after resuscitation, and plasma and hearts 
      were harvested for biochemical assays. Vehicle-treated mature mice exhibited 
      higher myocardial injury and higher levels of plasma biomarkers of cardiovascular 
      injury (endocan and follistatin) when compared with young mice. Cardiac cell 
      mitochondrial structure was also markedly impaired in vehicle-treated mature mice 
      when compared with young mice. At molecular analysis, an increase of the 
      phosphorylated catalytic subunit pAMPKalpha was associated with nuclear translocation 
      of the peroxisome proliferator-activated receptor gamma coactivator-alpha in young, but 
      not mature mice. No changes in autophagy were observed as evaluated by the 
      conversion of the light-chain (LC)3B-I protein to LC3B-II form. Treatment with 
      AICAR ameliorated myocardial damage in both age groups. However, AICAR 
      therapeutic effects were less effective in mature mice than young mice and 
      involved distinct mechanisms of action. Thus, our data demonstrate that during 
      hemorrhagic shock AMPK-dependent metabolic mechanisms are important for 
      mitigating myocardial injury. However, these mechanisms are less competent with 
      age.
FAU - Matsiukevich, Dzmitry
AU  - Matsiukevich D
AD  - *Department of Pediatrics, Division of Critical Care Medicine, Cincinnati 
      Children's Hospital Medical Center, Cincinnati, OhiodaggerDepartment of Surgery, 
      University of Cincinnati, Cincinnati, Ohio.
FAU - Piraino, Giovanna
AU  - Piraino G
FAU - Klingbeil, Lindsey R
AU  - Klingbeil LR
FAU - Hake, Paul W
AU  - Hake PW
FAU - Wolfe, Vivian
AU  - Wolfe V
FAU - O'Connor, Michael
AU  - O'Connor M
FAU - Zingarelli, Basilia
AU  - Zingarelli B
LA  - eng
GR  - R01 AG027990/AG/NIA NIH HHS/United States
GR  - R01 GM067202/GM/NIGMS NIH HHS/United States
GR  - R01 GM115973/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Biomarkers)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Age Factors
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/therapeutic use
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Blotting, Western
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Electron, Transmission
MH  - Mitochondria/drug effects/metabolism
MH  - Myocardium/*metabolism/ultrastructure
MH  - Ribonucleotides/*therapeutic use
MH  - Shock, Hemorrhagic/*drug therapy/*metabolism
PMC - PMC5167668
MID - NIHMS808261
COIS- Conflicts of Interest: None declared
EDAT- 2016/08/12 06:00
MHDA- 2018/02/21 06:00
PMCR- 2018/01/01
CRDT- 2016/08/12 06:00
PHST- 2016/08/12 06:00 [pubmed]
PHST- 2018/02/21 06:00 [medline]
PHST- 2016/08/12 06:00 [entrez]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.1097/SHK.0000000000000730 [doi]
PST - ppublish
SO  - Shock. 2017 Jan;47(1):70-78. doi: 10.1097/SHK.0000000000000730.