2017-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/644772摘要：慢性血栓栓塞性肺高壓（Chronic thromboembolic pulmonary hypertension，簡稱 CTEPH）的致病機轉主要是肺動脈內血栓的形成及血管內膜纖維化病變所造成，屬於第四類的肺高壓。可藉由外科手術的方式 (肺動脈內膜剝離手術，pulmonary endarterectomy, 簡稱PEA) 改善病患的病情；但CTEPH 的研究鮮少，造成致病機轉仍不明確。本團隊初步研究顯示，CTEPH 病人肺動脈血管內膜組織切片染色中collagen表現量顯著增加，且增厚血管內膜組織內皮細胞同時呈現 eNOS(內皮細胞標記)及ɑ-SM-actin(間質纖維母細胞標記)，推測內皮細胞間質轉化（EndMT）可能參與CTEPH 的病理。本研究目的要探討造成CTEPH 病理變化過程所引發的內皮細胞間質轉化機轉及其細胞間訊號傳遞調控相關路徑，其步驟如下: (1.) 收集CTEPH 病人手術前血液及PEA 手術後的肺動脈血管內血栓與增厚的纖維化血管內膜, 利用微陣列分析(Microarray)，探討內皮間質轉化（EndMT）相關過程在細胞分子層級的表現。 (2.) 分離與培養手術取出之肺動脈內膜的肺動脈內皮細胞，深入探討CTEPH 病人的肺動脈內皮細胞過度增殖是否與誘發血管內皮間質轉變（EndMT）的病理機轉及訊號傳遞有關。（3）利用CTEPH 病人肺動脈內皮細胞來探討其他類型的藥物是否具有抑制內皮間質轉化（EndMT）及訊號傳遞調控的功能。希冀能藉由此研究證實內皮間質轉化與CTEPH 病理機轉的相關性，為後續的基礎研究暨臨床治療提供更多的訊息。<br> Abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is an individual subtypeof pulmonary hypertension and characterized by unresolved intravascular thrombusformation and obliteration in the pulmonary arteries leading to severe pulmonaryhypertension. In our preliminary studies, we show that thrombofibrotic pulmonaryartery stenosis from CTEPH patients reveal significantly increased collagen byMasson’s trichrome stain. In the immunohistochemistry, the endothelial cellsrepresent eNOS (an endothelial marker) and ɑ-smooth muscle-actin (a mesenchymalmarker) in thrombofibrotic pulmonary artery stenosis to demonstrate that thedevelopment of endothelial-to-mesenchymal transition (EndMT) may be involved inCTEPH. However, the pathomechanisms underlying the development ofthrombofibrotic pulmonary artery stenosis remain largely unidentified. Wehypothesize that EndMT may play a critical role in the pathogenesis of CTEPH. Theaim of this study is to investigate the proteins and cell types involved in the signaltransduction of EndMT related to developing CTEPH. Our first aim of this proposalis to use thrombofibrotic pulmonary artery stenosis tissue from pulmonaryendarterectomy (PEA) to determine the genes by microarray, proteins and cell typesinvolved in EndMT related to developing CTEPH. Our second aim is to use humanpulmonary arterial endothelial cells to investigate whether hyperproliferativepulmonary arterial endothelial cells and triggered mesenchymal cells inendothelial-to-mesenchymal transition (EndMT) are involved in CTEPH. Our thirdaim is to find a novel therapeutic approach for CTEPH treatment by pursuing ourobservation that EndMT may play a crucial role in the pathogenesis of CTEPH.