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Investigating inherent functional differences between human cardiac fibroblasts cultured from non-diabetic and type 2 diabetic donors
Sedgwick, B. Riches-Suman, Kirsten Bageghni, S.A. O'Regan, D.J. Porter, K.E. Turner, N.A.
Sedgwick, B.
Riches-Suman, Kirsten
Bageghni, S.A.
O'Regan, D.J.
Porter, K.E.
Turner, N.A.
Publication Date
2014-08
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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
Open Access status
openAccess
Accepted for publication
2014-03-19
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Department
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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.
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.
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Article