PMID- 28478479
OWN - NLM
STAT- MEDLINE
DCOM- 20180410
LR  - 20181113
IS  - 1435-1803 (Electronic)
IS  - 0300-8428 (Print)
IS  - 0300-8428 (Linking)
VI  - 112
IP  - 4
DP  - 2017 Jul
TI  - Dissecting the role of myeloid and mesenchymal fibroblasts in age-dependent 
      cardiac fibrosis.
PG  - 34
LID - 10.1007/s00395-017-0623-4 [doi]
AB  - Aging is associated with increased cardiac interstitial fibrosis and diastolic 
      dysfunction. Our previous study has shown that mesenchymal fibroblasts in the 
      C57BL/6J (B6J) aging mouse heart acquire an inflammatory phenotype and produce 
      higher levels of chemokines. Monocyte chemoattractant protein-1 (MCP-1) secreted 
      by these aged fibroblasts promotes leukocyte uptake into the heart. Some of the 
      monocytes that migrate into the heart polarize into M2a macrophages/myeloid 
      fibroblasts. The number of activated mesenchymal fibroblasts also increases with 
      age, and consequently, both sources of fibroblasts contribute to fibrosis. Here, 
      we further investigate mechanisms by which inflammation influences activation of 
      myeloid and mesenchymal fibroblasts and their collagen synthesis. We examined 
      cardiac fibrosis and heart function in three aged mouse strains; we compared 
      C57BL/6J (B6J) with two other strains that have reduced inflammation via 
      different mechanisms. Aged C57BL/6N (B6N) hearts are protected from oxidative 
      stress and fibroblasts derived from them do not develop an inflammatory 
      phenotype. Likewise, these mice have preserved diastolic function. Aged MCP-1 
      null mice on the B6J background (MCP-1KO) are protected from elevated leukocyte 
      infiltration; they develop moderate but reduced fibrosis and diastolic 
      dysfunction. Based on these studies, we further delineated the role of resident 
      versus monocyte-derived M2a macrophages in myeloid-dependent fibrosis and found 
      that the number of monocyte-derived M2a (but not resident) macrophages correlates 
      with age-related fibrosis and diastolic dysfunction. In conclusion, we have found 
      that ROS and inflammatory mediators are necessary for activation of fibroblasts 
      of both developmental origins, and prevention of either led to better functional 
      outcomes.
FAU - Trial, JoAnn
AU  - Trial J
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, One Baylor Plaza, M.S. BCM620, Houston, TX, 
      77030, USA.
FAU - Heredia, Celia Pena
AU  - Heredia CP
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, One Baylor Plaza, M.S. BCM620, 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, One Baylor Plaza, M.S. BCM620, 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, One Baylor Plaza, M.S. BCM620, Houston, TX, 
      77030, USA.
AD  - Houston Methodist, Houston, TX, USA.
FAU - Cieslik, Katarzyna A
AU  - Cieslik KA
AD  - Division of Cardiovascular Sciences and the DeBakey Heart Center, Department of 
      Medicine, Baylor College of Medicine, One Baylor Plaza, M.S. BCM620, Houston, TX, 
      77030, USA. cieslik@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 - 20170506
PL  - Germany
TA  - Basic Res Cardiol
JT  - Basic research in cardiology
JID - 0360342
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
SB  - IM
MH  - Age Factors
MH  - Aging/genetics/metabolism/*pathology
MH  - Animals
MH  - Cardiomyopathies/genetics/metabolism/*pathology/physiopathology
MH  - Cell Communication
MH  - *Cell Lineage
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - Diastole
MH  - Fibroblasts/metabolism/*pathology
MH  - Fibrosis
MH  - Inflammation/genetics/metabolism/*pathology
MH  - Macrophage Activation
MH  - Macrophages/metabolism/*pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocardium/metabolism/*pathology
MH  - Oxidative Stress
MH  - Phenotype
MH  - Ventricular Dysfunction, Left/metabolism/pathology/physiopathology
MH  - Ventricular Function, Left
PMC - PMC5591578
MID - NIHMS901529
OTO - NOTNLM
OT  - Aging
OT  - Fibroblast
OT  - Fibrosis
OT  - Heart
OT  - Inflammation
COIS- CONFLICT OF INTEREST On behalf of all authors, the corresponding author states 
      that there is no conflict of interest.
EDAT- 2017/05/10 06:00
MHDA- 2018/04/11 06:00
PMCR- 2018/07/01
CRDT- 2017/05/08 06:00
PHST- 2017/03/29 00:00 [received]
PHST- 2017/04/27 00:00 [accepted]
PHST- 2017/05/08 06:00 [entrez]
PHST- 2017/05/10 06:00 [pubmed]
PHST- 2018/04/11 06:00 [medline]
PHST- 2018/07/01 00:00 [pmc-release]
AID - 10.1007/s00395-017-0623-4 [pii]
AID - 10.1007/s00395-017-0623-4 [doi]
PST - ppublish
SO  - Basic Res Cardiol. 2017 Jul;112(4):34. doi: 10.1007/s00395-017-0623-4. Epub 2017 
      May 6.