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    Investigating inherent functional differences between human cardiac fibroblasts cultured from non-diabetic and type 2 diabetic donors

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    Sedgwick B Cardiovasc Pathol 2014.pdf (295.3Kb)
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    Publication date
    2014-08
    Author
    Sedgwick, B.
    Riches-Suman, Kirsten
    Bageghni, S.A.
    O'Regan, D.J.
    Porter, K.E.
    Turner, N.A.
    Keyword
    Cardiac fibroblasts; Type I collagen; Human; Heart; Type 2 diabetes
    Rights
    © 2014 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
    Peer-Reviewed
    yes
    
    Metadata
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    Abstract
    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.
    URI
    http://hdl.handle.net/10454/10085
    Version
    Accepted Manuscript
    Citation
    Sedgwick B, Riches-Suman K, Bageghni SA et al (2014) Investigating inherent functional differences between human cardiac fibroblasts cultured from non-diabetic and type 2 diabetic donors. Cardiovascular Patholology. 23(4): 204-210.
    Link to publisher’s version
    http://dx.doi.org/10.1016/j.carpath.2014.03.004
    Type
    Article
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    Life Sciences Publications

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