PMID- 24746387
OWN - NLM
STAT- MEDLINE
DCOM- 20150512
LR  - 20211203
IS  - 1879-1336 (Electronic)
IS  - 1054-8807 (Linking)
VI  - 23
IP  - 4
DP  - 2014 Jul-Aug
TI  - Investigating inherent functional differences between human cardiac fibroblasts 
      cultured from nondiabetic and Type 2 diabetic donors.
PG  - 204-10
LID - S1054-8807(14)00032-5 [pii]
LID - 10.1016/j.carpath.2014.03.004 [doi]
AB  - INTRODUCTION: Type 2 diabetes mellitus (T2DM) promotes adverse myocardial 
      remodeling and increased risk of heart failure; effects that can occur 
      independently of hypertension or coronary artery disease. As cardiac fibroblasts 
      (CFs) are key effectors of myocardial remodeling, we investigated whether 
      inherent phenotypic differences exist in CF derived from T2DM donors compared 
      with cells from nondiabetic (ND) donors. METHODS: Cell morphology (cell area), 
      proliferation (cell counting over 7-day period), insulin signaling [phospho-Akt 
      and phospho-extracellular signal-regulated kinase (ERK) Western blotting], and 
      mRNA expression of key remodeling genes [real-time reverse 
      transcription-polymerase chain reaction (RT-PCR)] were compared in CF cultured 
      from atrial tissue from 14 ND and 12 T2DM donors undergoing elective coronary 
      artery bypass surgery. RESULTS: The major finding was that Type I collagen 
      (COL1A1) mRNA levels were significantly elevated by twofold in cells derived from 
      T2DM donors compared with those from ND donors; changes reflected at the protein 
      level. T2DM cells had similar proliferation rates but a greater variation in cell 
      size and a trend towards increased cell area compared with ND cells. 
      Insulin-induced Akt and ERK phosphorylation were similar in the two cohorts of 
      cells. CONCLUSION: CF from T2DM individuals possess an inherent profibrotic 
      phenotype that may help to explain the augmented cardiac fibrosis observed in 
      diabetic patients. MINI SUMMARY: We investigated whether inherent phenotypic 
      differences exist between CF cultured from donors with or without Type 2 
      diabetes. Cell morphology, proliferation, insulin signaling, and gene expression 
      were compared between multiple cell populations. The major finding was that Type 
      I collagen levels were elevated in fibroblasts from diabetic donors, which may 
      help explain the augmented cardiac fibrosis observed with diabetes.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Sedgwick, Bryony
AU  - Sedgwick B
AD  - Division of Cardiovascular and Diabetes Research, School of Medicine, University 
      of Leeds, Leeds, UK.
FAU - Riches, Kirsten
AU  - Riches K
AD  - Division of Cardiovascular and Diabetes Research, School of Medicine, University 
      of Leeds, Leeds, UK; Multidisciplinary Cardiovascular Research Centre (MCRC), 
      University of Leeds, Leeds, UK.
FAU - Bageghni, Sumia A
AU  - Bageghni SA
AD  - Division of Cardiovascular and Diabetes Research, School of Medicine, University 
      of Leeds, Leeds, UK; Multidisciplinary Cardiovascular Research Centre (MCRC), 
      University of Leeds, Leeds, UK.
FAU - O'Regan, David J
AU  - O'Regan DJ
AD  - Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, 
      Leeds, UK; Department of Cardiac Surgery, The Yorkshire Heart Centre, Leeds 
      General Infirmary, Leeds, UK.
FAU - Porter, Karen E
AU  - Porter KE
AD  - Division of Cardiovascular and Diabetes Research, School of Medicine, University 
      of Leeds, Leeds, UK; Multidisciplinary Cardiovascular Research Centre (MCRC), 
      University of Leeds, Leeds, UK.
FAU - Turner, Neil A
AU  - Turner NA
AD  - Division of Cardiovascular and Diabetes Research, School of Medicine, University 
      of Leeds, Leeds, UK; Multidisciplinary Cardiovascular Research Centre (MCRC), 
      University of Leeds, Leeds, UK. Electronic address: n.a.turner@leeds.ac.uk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140326
PL  - United States
TA  - Cardiovasc Pathol
JT  - Cardiovascular pathology : the official journal of the Society for Cardiovascular 
      Pathology
JID - 9212060
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type I, alpha 1 Chain)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Atrial Remodeling/genetics/physiology
MH  - Cell Proliferation
MH  - Cell Size
MH  - Cells, Cultured
MH  - Collagen Type I/genetics/metabolism
MH  - Collagen Type I, alpha 1 Chain
MH  - Diabetes Mellitus, Type 2/genetics/metabolism/*pathology
MH  - Fibroblasts/cytology/metabolism/pathology
MH  - Fibrosis
MH  - Humans
MH  - Interleukin-1alpha/metabolism
MH  - MAP Kinase Signaling System
MH  - Myocardium/cytology/metabolism/*pathology
MH  - Phenotype
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptor, Insulin/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - Cardiac fibroblasts
OT  - Heart
OT  - Human
OT  - Type 2 diabetes
OT  - Type I collagen
EDAT- 2014/04/22 06:00
MHDA- 2015/05/13 06:00
CRDT- 2014/04/22 06:00
PHST- 2013/10/17 00:00 [received]
PHST- 2014/03/19 00:00 [revised]
PHST- 2014/03/19 00:00 [accepted]
PHST- 2014/04/22 06:00 [entrez]
PHST- 2014/04/22 06:00 [pubmed]
PHST- 2015/05/13 06:00 [medline]
AID - S1054-8807(14)00032-5 [pii]
AID - 10.1016/j.carpath.2014.03.004 [doi]
PST - ppublish
SO  - Cardiovasc Pathol. 2014 Jul-Aug;23(4):204-10. doi: 10.1016/j.carpath.2014.03.004. 
      Epub 2014 Mar 26.