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Role of Biochemical and Biophysical Factors on Endothelial-to-Mesenchymal Transformation

机译:生化和生物物理因素在内皮细胞向间充质转化中的作用

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The prevalence of calcific aortic valve disease is rising and is only treatable by surgical replacement of the stenotic valve. There is currently no biomarker or pharmacological therapy available for the treatment of early aortic valve disease and this is largely due to our limited understanding of the disease mechanisms. One potential mechanism of valve repair and potentially early valve disease is endothelial-to-mesenchymal transformation (EndMT), the initiating event of valvulogenesis. Our preliminary work has shown that extracellular matrix (ECM) composition that mimics diseased valve conditions strongly stimulates mesenchymal transformation. EndMT may be a mechanism for signaling valve interstitial cells toward either valve regeneration or disease and growing evidence indicates that communication between the interstitial cells and the endothelial cells is essential for valve homeostasis. Unfortunately, there is currently no known unifying mechanism of valve disease that connects endothelial cell dysfunction, interstitial cell differentiation, and pathological matrix remodeling. Our research seeks to reveal this mechanism using novel, unique to our laboratory tools, greatly facilitating the discovery and new clinical strategies for controlling early-detected valve disease with minimally invasive interventions.
机译:钙化主动脉瓣疾病的患病率正在上升,只能通过外科手术更换狭窄瓣膜来治疗。目前尚无用于早期主动脉瓣疾病治疗的生物标志物或药物治疗方法,这在很大程度上是由于我们对疾病机制的了解有限。瓣膜修复和潜在早期瓣膜疾病的一种潜在机制是内皮向间充质转化(EndMT),这是瓣膜形成的起始事件。我们的初步工作表明,模拟患病瓣膜状况的细胞外基质(ECM)成分会强烈刺激间质转化。 EndMT可能是一种向瓣膜间质细胞发出信号指示瓣膜再生或疾病的机制,越来越多的证据表明,间质细胞与内皮细胞之间的通讯对于瓣膜的动态平衡至关重要。不幸的是,目前尚无瓣膜疾病的统一机制将内皮细胞功能障碍,间质细胞分化和病理性基质重塑联系起来。我们的研究旨在通过新颖,独特的实验室工具来揭示这种机制,从而极大地促进发现和新的临床策略,从而通过微创干预来控制早期发现的瓣膜疾病。

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