PMID- 28826664
OWN - NLM
STAT- MEDLINE
DCOM- 20180514
LR  - 20181211
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 111
DP  - 2017 Oct
TI  - Aicar treatment reduces interstitial fibrosis in aging mice: Suppression of the 
      inflammatory fibroblast.
PG  - 81-85
LID - S0022-2828(17)30283-3 [pii]
LID - 10.1016/j.yjmcc.2017.08.003 [doi]
AB  - In 2030, elderly people will represent 20% of the United States population. Even 
      now, chronic cardiac diseases, especially heart failure with preserved systolic 
      function (HFpEF), are the most expensive DRGs for Medicare. Progressive 
      interstitial fibrosis in the aging heart is well recognized as an important 
      component of HFpEF. Our recent studies suggested an important pathophysiologic 
      role for reduced TGF-beta receptor 1 (TGFbetaR1) signaling in mesenchymal stem cells 
      (MSCs) and their mesenchymal fibroblast progeny in the development of 
      interstitial fibrosis. This report arises from our previous studies, which 
      suggest that an inflammatory phenotype exists in these mesenchymal fibroblasts as 
      a result of a reduced TGF-beta-Smad-dependent pathway but upregulated 
      farnesyltransferase (FTase)-Ras-Erk signaling. In this report we provide evidence 
      for a therapeutic approach that downregulates Erk activation through an adenosine 
      monophosphate-activated kinase (AMPK) pathway. Aging C57BL/6J mice were treated 
      with AICAR (an AMPK activator) for a 30-day period. This treatment suppressed 
      excessive monocyte chemoattractant protein-1 (MCP-1) generation, which diminished 
      leukocyte infiltration and in consequence suppressed the formation of 
      macrophage-derived myeloid fibroblasts. Interestingly, the number of mesenchymal 
      fibroblasts was also reduced. In addition, we observed changes in extracellular 
      matrix (ECM) deposition, specifically that collagen type I and the alternatively 
      spliced variant of fibronectin (EDA) expressions were reduced. These data suggest 
      that the upregulation of AMPK activity is a potential therapeutic approach to 
      fibrosis in the aging heart.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Cieslik, Katarzyna A
AU  - Cieslik KA
AD  - Division of Cardiovascular Sciences, DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, Houston, TX, United States; Houston 
      Methodist Hospital, Houston, TX, United States.
FAU - Trial, JoAnn
AU  - Trial J
AD  - Division of Cardiovascular Sciences, DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, Houston, TX, United States; Houston 
      Methodist Hospital, Houston, TX, United States.
FAU - Entman, Mark L
AU  - Entman ML
AD  - Division of Cardiovascular Sciences, DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, Houston, TX, United States; Houston 
      Methodist Hospital, Houston, TX, United States. Electronic address: 
      mentman@bcm.edu.
LA  - eng
GR  - R01 HL089792/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170804
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Biomarkers)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - Aging/*pathology
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Cell Count
MH  - Fibroblasts/drug effects/*pathology
MH  - Fibrosis
MH  - Inflammation/*pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Myocardium/pathology
MH  - Ribonucleotides/*pharmacology
PMC - PMC5600709
MID - NIHMS900124
OTO - NOTNLM
OT  - AMPK
OT  - Fibroblast
OT  - Fibrosis
OT  - Heart
OT  - Macrophage
EDAT- 2017/08/23 06:00
MHDA- 2018/05/15 06:00
PMCR- 2018/10/01
CRDT- 2017/08/23 06:00
PHST- 2017/05/09 00:00 [received]
PHST- 2017/08/01 00:00 [revised]
PHST- 2017/08/03 00:00 [accepted]
PHST- 2017/08/23 06:00 [pubmed]
PHST- 2018/05/15 06:00 [medline]
PHST- 2017/08/23 06:00 [entrez]
PHST- 2018/10/01 00:00 [pmc-release]
AID - S0022-2828(17)30283-3 [pii]
AID - 10.1016/j.yjmcc.2017.08.003 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2017 Oct;111:81-85. doi: 10.1016/j.yjmcc.2017.08.003. Epub 
      2017 Aug 4.