PMID- 26718722
OWN - NLM
STAT- MEDLINE
DCOM- 20161111
LR  - 20181202
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 91
DP  - 2016 Feb
TI  - Mesenchymal stem cell-derived inflammatory fibroblasts mediate interstitial 
      fibrosis in the aging heart.
PG  - 28-34
LID - S0022-2828(15)30156-5 [pii]
LID - 10.1016/j.yjmcc.2015.12.017 [doi]
AB  - Pathologic fibrosis in the aging mouse heart is associated with dysregulated 
      resident mesenchymal stem cells (MSC) arising from reduced stemness and aberrant 
      differentiation into dysfunctional inflammatory fibroblasts. Fibroblasts derived 
      from aging MSC secrete higher levels of 1) collagen type 1 (Col1) that directly 
      contributes to fibrosis, 2) monocyte chemoattractant protein-1 (MCP-1) that 
      attracts leukocytes from the blood and 3) interleukin-6 (IL-6) that facilitates 
      transition of monocytes into myeloid fibroblasts. The transcriptional activation 
      of these proteins is controlled via the farnesyltransferase (FTase)-Ras-Erk 
      pathway. The intrinsic change in the MSC phenotype acquired by advanced age is 
      specific for the heart since MSC originating from bone wall (BW-MSC) or 
      fibroblasts derived from them were free of these defects. The potential 
      therapeutic interventions other than clinically approved strategies based on 
      findings presented in this review are discussed as well. This article is a part 
      of a Special Issue entitled "Fibrosis and Myocardial Remodeling".
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Trial, JoAnn
AU  - Trial J
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, Houston, TX, United States.
FAU - Entman, Mark L
AU  - Entman ML
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, Houston, TX, United States; Houston 
      Methodist, Houston, TX, United States.
FAU - Cieslik, Katarzyna A
AU  - Cieslik KA
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, Houston, TX, United States. Electronic 
      address: cieslik@bcm.edu.
LA  - eng
GR  - R01 HL089792/HL/NHLBI NIH HHS/United States
GR  - R01HL089792/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20151222
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Cytokines)
RN  - 0 (Insulin)
RN  - 0 (RASGRF1 protein, human)
RN  - 0 (ras-GRF1)
RN  - EC 2.5.- (Alkyl and Aryl Transferases)
RN  - EC 2.5.1.- (p21(ras) farnesyl-protein transferase)
SB  - IM
MH  - Aging/metabolism/*pathology
MH  - Alkyl and Aryl Transferases/genetics/metabolism
MH  - Animals
MH  - Cytokines/genetics/metabolism
MH  - Epigenesis, Genetic
MH  - Fibroblasts/*cytology/metabolism
MH  - Fibrosis
MH  - Humans
MH  - Inflammation
MH  - Insulin/genetics/metabolism
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Mice
MH  - Myeloid Cells/*cytology/metabolism
MH  - Myocardium/metabolism/*pathology
MH  - Signal Transduction
MH  - ras-GRF1/genetics/metabolism
PMC - PMC4764495
MID - NIHMS750050
OTO - NOTNLM
OT  - Aging
OT  - Fibrocyte
OT  - Inflammatory fibroblast
OT  - MSC
OT  - Myeloid fibroblasts
OT  - RasGrf1
EDAT- 2016/01/01 06:00
MHDA- 2016/11/12 06:00
PMCR- 2017/02/01
CRDT- 2016/01/01 06:00
PHST- 2015/09/10 00:00 [received]
PHST- 2015/12/08 00:00 [revised]
PHST- 2015/12/20 00:00 [accepted]
PHST- 2016/01/01 06:00 [entrez]
PHST- 2016/01/01 06:00 [pubmed]
PHST- 2016/11/12 06:00 [medline]
PHST- 2017/02/01 00:00 [pmc-release]
AID - S0022-2828(15)30156-5 [pii]
AID - 10.1016/j.yjmcc.2015.12.017 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2016 Feb;91:28-34. doi: 10.1016/j.yjmcc.2015.12.017. Epub 
      2015 Dec 22.