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標題: | 波浪狀纖維結構促進早衰素表現血管平滑肌細胞收縮型 Wavy Fiber Structure Improves Contractile Phenotype of Progerin-expressing Vascular Smooth Muscle Cells |
作者: | 林俊宇 Chun-Yu Lin |
指導教授: | 趙本秀 Pen-Hsiu Chao |
關鍵字: | 微結構,動脈,血管平滑肌表現型多元性,仿生纖維平台,早衰素, microstructure,artery,VSMC plasticity,biomimetic scaffold,topography,progerin, |
出版年 : | 2022 |
學位: | 碩士 |
摘要: | 彈性動脈緩衝來自心搏的血壓波動以穩定提供器官血液,此彈性機械性質來自血管壁間質之環繞波浪狀微結構,而老化或受傷的動脈因彈性組織纖維結構與成分的改變導致硬度上升與功能受損。血管平滑肌細胞維持動脈結構與功能恆定,在成長、修復或疾病過程中,血管平滑肌細胞可從收縮型轉變為合成型以促進細胞增殖與胞外基質分泌,此表現型調控若失衡可能誘發血管修復不良與血管疾病惡化;目前雖有不少研究探討環境化學因子對血管平滑肌表現型的調控,不過組織纖維結構本身對血管平滑肌的影響卻尚未釐清。本研究以電紡絲技術製造仿生纖維,模擬健康動脈的捲曲或是老化受傷動脈的直線結構,以期釐清結構型態對細胞的調控。此外,在疾病動物模式發現表現早衰素的血管平滑肌細胞會加速血管的病變,因此我們也研究早衰素對血管平滑肌表現型的影響,並綜合性探討組織纖維排列與早衰素對血管平滑肌的調控。研究結果發現,捲曲纖維結構雖對正常血管平滑肌的效應微弱,但對帶有早衰素的血管平滑肌細胞則效果顯著。捲曲纖維結構除可緩衝血壓波動,本研究也指出其對血管平滑肌表現型調節的重要性;同時,探索調控血管恆定對了解血管疾病機轉高度重要,而我們的仿生纖維平台適用於發展血管疾病的模擬並有助於新藥的開發。 Elastic arteries smoothen the pulsatile blood flow from cardiac output to nourish the organs. Elastic fibers in arterial wall form circumferentially wavy microstructure, contributing to the mechanical functionality. In aged or injured arteries, elastic fibers undergo morphological and compositional changes, resulting in loss of tissue function. In the arterial wall, contractile vascular smooth muscle cells (VSMCs) maintain the mechanical functionality of the tissue. During vessel growth, repair, or pathogenesis, VSMCs become proliferative and synthesize abundant matrix components, known as the synthetic phenotype. Imbalanced VSMC plasticity induces adverse arterial remodeling and progression of vascular diseases. Environmental cues regulate phenotypic flexibility of VSMC, but the roles of matrix organization remain largely unknown. To address the influence of fiber structure on VSMC phenotype, we established VSMC culture in straight or wavy scaffold, which structurally mimics the aged/injured or healthy arteries. Additionally, we used progerin-expressing VSMCs, which drive vascular alternation in disease model animals, to investigate progerin and topography interaction. We found that while wavy topography slightly promoted contractile phenotype of wild-type (WT) VSMC, the effect was more robust in progerin-expressing VSMC. Our study indicated that wavy fiber structure played significant roles in regulating VSMC phenotype besides its mechanical contribution. Identifying regulatory factors involved in arterial homeostasis will help uncover mechanism of vascular pathology, and our biomimetic scaffold offers a relevant platform for disease modeling as well as new drug discovery. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/85774 |
DOI: | 10.6342/NTU202200741 |
全文授權: | 同意授權(全球公開) |
電子全文公開日期: | 2024-03-22 |
顯示於系所單位: | 醫學工程學研究所 |
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ntu-110-2.pdf | 4.12 MB | Adobe PDF | 檢視/開啟 |
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