Differential responsiveness of human atrial and ventricular fibroblasts to serum-induced proliferation and its inhibition by simvastatin


Aurora Research Institute


Background: Fibroblasts, the most abundant cells in the heart, contribute to cardiac fibrosis and to the substrate for arrhythmogenesis and, therefore, are potential targets for prevention of arrhythmic cardiac remodeling. Chamber-specific differences in the responsiveness of fibroblasts from the atria and ventricles toward cytokines and growth factor have been demonstrated in animal models, but it is unclear if similar differences exist in human cardiac fibroblasts and whether drugs affect their proliferation differentially.

Methods: Differences between human atrial and ventricular fibroblasts obtained from patients undergoing cardiac surgery in seruminduced proliferation, DNA synthesis [5-ethynyl-2’-deoxyuridine (EdU) incorporation assay], cell cycle progression (flow cytometry), and expression of cyclins (A, D1, D2, D3 and E) mRNA (RT-PCR) and protein (immunoblotting) expression and their inhibition by simvastatin were determined.

Results:The serum-induced proliferation of human atrial fibroblasts was 3.1 (p

Conclusions: Thus, chamber-specific differences exist in the human heart, with atrial fibroblasts having higher proliferative capacity and being more sensitive to simvastatin-mediated inhibition through the HMG-CoA reductase pathway. This atrial selective effect may be useful in preventing excessive atrial fibrosis without inhibiting adaptive ventricular remodeling during myocardial injury.

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