Introduction: Type 2 diabetes mellitus (T2DM) promotes adverse myocardial remodelling and increased risk of heart failure; effects that can occur independently of hypertension or coronary artery disease. As cardiac fibroblasts (CF) are key effectors of myocardial remodelling, we investigated whether inherent phenotypic differences exist in CF derived from T2DM donors compared with cells from non-diabetic (ND) donors. Methods:Cell morphology (cell area), proliferation (cell counting over 7-day period), insulin signalling (phospho-Akt and phospho-ERK Western blotting) and mRNA expression of key remodelling genes (real-time 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 2-fold 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. Insulininduced Akt and ERK phosphorylation were similar in the two cohorts of cells. Conclusion:CF from T2DM individuals possess an inherent pro-fibrotic phenotype that may help to explain the augmented cardiac fibrosis observed in diabetic patients. Mini SummaryWe investigated whether inherent phenotypic differences exist between cardiac fibroblasts cultured from donors with or without Type 2 diabetes. Cell morphology, proliferation, insulin signalling 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.

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