Abstract P2098: The Effect Of Cyclic Stretch On Cardiac Fibroblasts

• DOI: 10.1161/res.133.suppl_1.p2098
• Publication Date: 2023-10-13T13:06:51Z
• Authors: Fjodor Bekedam; Marisa Smit; rowan Smal; Anton Vonk Noorde...; Harm J Bogaard; Marie J Goumans; Frances S De; Aida Llucia-Valld...
• Keywords: Myofibroblast; Cardiac Fibrosis; Transdifferentiation

Introduction: Cardiac fibrosis is the accumulation of extracellular matrix proteins in interstitium and contributes to heart failure. The main source cardiac fibroblasts (cFBs), which are activated as a result pressure overload. Activated fibroblasts, also known myofibroblasts, express α-smooth muscle actin (α-SMA) have an increased production collagen. Here, objective was study behavior induced pluripotent stem cell (iPSC) derived cFBs response pro-fibrotic cytokines mechanical stress. Methods: Confluent iPSC monolayers were differentiated into using protocol Figure 1A. Afterwards, cells exposed 10 ng/ml transforming growth factor β (TGFβ) 10% cyclic stretch at 1 Hz for 3 days Flexcell FX-6000 system. Results: iPSC-cFBs had fibroblast-like morphology. Furthermore, presence ( GATA4, TCF21 ) fibroblast VIM, PDGFRα, DDR2 markers gene protein levels confirmed cFB identity. TGF-β stimulation resulted mRNA α-SMA. Additionally, stretching reduced collagen expression (Fig. 1B/C). able protect from stimulation, significantly reducing α-SMA levels. This associated with decreased downstream targets PAI1). Conclusion: Cyclic reduces activation can against resulting transdifferentiation myofibroblasts.