Statin therapy alters the transcriptome of ventricular fibroblasts from human failing heart
Ross G, Edwards S, Rizvi F, et al. Statin therapy alters the transcriptome of ventricular fibroblasts from human failing heart. Poster presented at: Basic Cardiovascular Sciences 2017 Scientific Sessions; July 10-13, 2017; Portland, Oregon.
Poster presented at: Basic Cardiovascular Sciences 2017 Scientific Sessions; July 10-13, 2017; Portland, Oregon.
Introduction: The mechanical and electrical dysfunction in heart failure (HF) is associated with excessive cardiac fibrosis (CF). Activation of human ventricular fibroblasts (hVF) and transdifferentiation to myofibroblasts underlies the increased CF. We recently reported that statin therapy reduced differentiation of hVF in HF patients. However, the underlying mechanism is not known. Therefore, we studied the effect of statin therapy on the transcriptome of hVF from HF patients. Hypothesis: We tested the hypothesis that statin therapy alters the expression of differentiation associated transcription factors (TF) in hVFs from HF patients.
Methods:Primary cultures of hVF obtained from HF patients undergoing left ventricular assist device implantation either under statin therapy for at least 1 year (n=3) or not (n=3). The extent of transcriptomic changes induced by statin therapy in hVFs was studied from total RNA using RT2 ProfilerTM PCR array - human transcription factors (Qiagen, Catalog No: PAHS-075Z ) run on Roche LightCycler 96-well block. Fold change was calculated by 2-ΔΔCt method. Data were analyzed by Student’s t test, and P value
Results:Out of the 84 related genes profiled, statin therapy upregulated significantly (P
Conclusion: Statin therapy mitigates differentiation of hVFs from human failing heart patients by associated changes in the transcriptome. Selective targeting of hVF transcription factor may be a potential therapeutic strategy to de-differentiate myofibroblasts and mitigate the progression of CF and HF.