Abstract 13352: Differential Response of Healthy Endocardial Cells versus Endocardial Fibroelastosis-Derived Cells to Flow Alterations and Statins
Circulation(2022)
摘要
Introduction: Endocardial Fibroelastosis (EFE) is a subendocardial thickening of organized collagen and elastin layers restricting the ventricle. It has been linked to flow disturbances in congenital heart defects. Endothelial-to-mesenchymal transition (EndMT) has been identified as the underlying mechanism for EFE and also plays a central role in other diseases such as atherosclerosis where statins (e. g. atorvastatin) have been successfully used as EndMT-inhibitors. This study sought to establish a causal relationship between flow and EndMT, and to determine the protective effects of atorvastatin. Methods: Healthy endocardial endothelial cells (EECs) and EFE-derived EECs were exposed to either flow stagnation (≤5dynes/cm 2 ) with and without atorvastatin (0.5μmol/l) or physiological flow (~10dynes/cm 2 ) using a flow pump system (ibidi). Active EndMT (double staining with αSMA and CD31/VE-Cadherin) and collagen production was determined by immunohistochemical staining. Results: In healthy EECs (n=4), flow stagnation induced EndMT and collagen production which was significantly ameliorated by physiological flow (n=3, p<0.001, Fig. 1A+C). In contrast, physiological flow resulted in an increase in collagen production by 89% (n=8, p<0.001, Fig. 1D) in EFE-derived EECs. Under flow stagnation, atorvastatin inhibited EndMT (reduction by 39%, p<0.001, Fig. 1A) and collagen production in healthy EECs (reduction by 9%, p<0.001, Fig. 1C). This effect was blunted in EFE-derived EECs regarding EndMT reduction (17%, p<0.001, Fig. 1B), with no effect on collagen. Conclusion: Physiological flow and atorvastatin protect healthy EECs from EndMT but only the latter is beneficial for EFE-derived EECs. Thus, statins potentially offer a preventative treatment for EFE patients with flow stagnation. This study revealed a profound difference in the response to flow of healthy and EFE-derived EECs, indicating an intrinsic predisposition to EndMT in these patients.
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关键词
healthy endocardial cells,fibroelastosis-derived
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