PMID- 24184998
OWN - NLM
STAT- MEDLINE
DCOM- 20141201
LR  - 20211021
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 70
DP  - 2014 May
TI  - Adverse fibrosis in the aging heart depends on signaling between myeloid and 
      mesenchymal cells; role of inflammatory fibroblasts.
PG  - 56-63
LID - S0022-2828(13)00316-7 [pii]
LID - 10.1016/j.yjmcc.2013.10.017 [doi]
AB  - Aging has been associated with adverse fibrosis. Here we formulate a new 
      hypothesis and present new evidence that unresponsiveness of mesenchymal stem 
      cells (MSC) and fibroblasts to transforming growth factor beta (TGF-beta), due to 
      reduced expression of TGF-beta receptor I (TbetaRI), provides a foundation for cardiac 
      fibrosis in the aging heart via two mechanisms. 1) TGF-beta promotes expression of 
      Nanog, a transcription factor that retains MSC in a primitive state. In MSC 
      derived from the aging heart, Nanog expression is reduced and therefore MSC 
      gradually differentiate and the number of mesenchymal fibroblasts expressing 
      collagen increases. 2) As TGF-beta signaling pathway components negatively regulate 
      transcription of monocyte chemoattractant protein-1 (MCP-1), a reduced expression 
      of TbetaRI prevents aging mesenchymal cells from shutting down their own MCP-1 
      expression. Elevated MCP-1 levels that originated from MSC attract 
      transendothelial migration of mononuclear leukocytes from blood to the tissue. 
      MCP-1 expressed by mesenchymal fibroblasts promotes further migration of 
      monocytes and T lymphocytes away from the endothelial barrier and supports the 
      monocyte transition into macrophages and finally into myeloid fibroblasts. Both 
      myeloid and mesenchymal fibroblasts contribute to fibrosis in the aging heart via 
      collagen synthesis. This article is part of a Special Issue entitled 
      "Myocyte-Fibroblast Signalling in Myocardium ".
CI  - (c) 2013. Published by Elsevier Ltd. All rights reserved.
FAU - Cieslik, Katarzyna A
AU  - Cieslik KA
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, and Houston Methodist, Houston, TX 77030, 
      USA. Electronic address: cieslik@bcm.edu.
FAU - Trial, JoAnn
AU  - Trial J
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, and Houston Methodist, Houston, TX 77030, 
      USA.
FAU - Crawford, Jeffrey R
AU  - Crawford JR
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, and Houston Methodist, Houston, TX 77030, 
      USA.
FAU - Taffet, George E
AU  - Taffet GE
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, and Houston Methodist, Houston, TX 77030, 
      USA.
FAU - Entman, Mark L
AU  - Entman ML
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, and Houston Methodist, Houston, TX 77030, 
      USA. Electronic address: mentman@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 - 20131031
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Homeodomain Proteins)
RN  - 0 (NANOG protein, human)
RN  - 0 (Nanog Homeobox Protein)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Aging/*metabolism/pathology
MH  - Cell Differentiation
MH  - Collagen/genetics/metabolism
MH  - Fibroblasts/*metabolism/pathology
MH  - Fibrosis/*metabolism/pathology/physiopathology
MH  - Gene Expression Regulation
MH  - Homeodomain Proteins/genetics/metabolism
MH  - Humans
MH  - Mesenchymal Stem Cells/*metabolism/pathology
MH  - Monocytes/metabolism/pathology
MH  - Myocardium/metabolism/pathology
MH  - Nanog Homeobox Protein
MH  - Receptors, Transforming Growth Factor beta/genetics/metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes/metabolism/pathology
MH  - Transforming Growth Factor beta/genetics/metabolism
PMC - PMC3995828
MID - NIHMS537504
OTO - NOTNLM
OT  - Aging
OT  - Inflammatory fibroblast
OT  - MCP-1
OT  - Mesenchymal stem cell
OT  - TGF-beta
COIS- Disclosure statement This research was conducted in the absence of any commercial 
      or financial relationships that could be construed as a potential conflict of 
      interest.
EDAT- 2013/11/05 06:00
MHDA- 2014/12/15 06:00
PMCR- 2015/05/01
CRDT- 2013/11/05 06:00
PHST- 2013/08/12 00:00 [received]
PHST- 2013/10/02 00:00 [revised]
PHST- 2013/10/22 00:00 [accepted]
PHST- 2013/11/05 06:00 [entrez]
PHST- 2013/11/05 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2015/05/01 00:00 [pmc-release]
AID - S0022-2828(13)00316-7 [pii]
AID - 10.1016/j.yjmcc.2013.10.017 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2014 May;70:56-63. doi: 10.1016/j.yjmcc.2013.10.017. Epub 
      2013 Oct 31.