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- W2980349849 abstract "Cardiac fibrosis is a common feature of heart failure independent of etiology. Although much is known about initiation of fibrosis in acute injury, factors leading to the persistence of fibrosis are poorly understood. We sought to determine if cardiac fibroblasts are necessary for the persistence of fibrosis by ablating resident cardiac fibroblasts in a mouse model of cardiac fibrosis. Methods: We generated mice with inducible ablation of cardiac fibroblasts (fb) by crossing the tcf21-cre gene into a MerCreMer-DTA mouse. These mice were then crossed into SR-uPA transgene which promotes diffuse interstitial fibrosis by 12 weeks of age. Control tcf21-DTA and tcf-21-DTA-SRuPA mice were treated with tamoxifen for 1-4 weeks to activate DTA and ablate cardiac fibroblasts. Echocardiography, histology and qPCR of isolated fb and macrophages (mac) was performed. Results: Treatment of wildtype tcf21-DTA mice with tamoxifen for 1-4 weeks resulted in a decrease in alpha-SMA positive cells in the heart but no change in left ventricular size or function. There was no excess mortality. Hearts showed no evidence of increased inflammation or fibrosis. Tcf21-DTA-SRuPA mice were viable but exhibited increased mortality starting at 10 days following initiation of tamoxifen. There were no changes in echocardiographic parameters, histologic inflammation or fibrosis. Fb had no change in expression of Col1a1 normalized to GAPDH. However, mac from Tcf21-DTA-SRuPA mice had a significant decrease in expression of M2 genes Arg1 and YM1. Conclusion: Ablation of fibroblasts was toxic to mice with established fibrosis, without changes in cardiac structure or function. Mac phenotype shifted from pro-fibrotic/M2 to pro-inflammatory/M1 with fibroblast ablation. These data point to important compensatory mechanisms that may maintain fibrosis in the heart." @default.
- W2980349849 created "2019-10-25" @default.
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- W2980349849 date "2019-08-02" @default.
- W2980349849 modified "2023-10-16" @default.
- W2980349849 title "Abstract 527: Cardiac Fibroblast Ablation in Chronic Fibrosis" @default.
- W2980349849 doi "https://doi.org/10.1161/res.125.suppl_1.527" @default.
- W2980349849 hasPublicationYear "2019" @default.
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