title: Investigating inherent functional differences between human cardiac fibroblasts cultured from nondiabetic and Type 2 diabetic donors.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  CF from T2DM individuals possess an inherent profibrotic phenotype that may help to explain the augmented cardiac fibrosis observed in diabetic patients.
  
  
  BACKGROUND
  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.
authors.affiliation: Division of Cardiovascular and Diabetes Research, School of Medicine, University of Leeds, Leeds, UK.
authors.forename: Bryony
authors.initials: B
authors.lastname: Sedgwick
authors.affiliation: Division of Cardiovascular and Diabetes Research, School of Medicine, University of Leeds, Leeds, UK; Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds, UK.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Riches
authors.affiliation: Division of Cardiovascular and Diabetes Research, School of Medicine, University of Leeds, Leeds, UK; Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds, UK.
authors.forename: Sumia A
authors.initials: SA
authors.lastname: Bageghni
authors.affiliation: Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds, UK; Department of Cardiac Surgery, The Yorkshire Heart Centre, Leeds General Infirmary, Leeds, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: O'Regan
authors.affiliation: Division of Cardiovascular and Diabetes Research, School of Medicine, University of Leeds, Leeds, UK; Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds, UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Porter
authors.affiliation: 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.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Turner
mesh_terms: D064752:Atrial Remodeling / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D048429:Cell Size; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D053582:Interleukin-1alpha; D012333:RNA, Messenger; D011972:Receptor, Insulin
keywords: Cardiac fibroblasts; Heart; Human; Type 2 diabetes; Type I collagen