2023 Fiscal Year Final Research Report

Influence of shear stress on human aortic endothelial cell/smooth muscle cell interaction in bicuspid aortic valve aortopathy

Research Project

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Project/Area Number	20K09154
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55030:Cardiovascular surgery-related
Research Institution	Jichi Medical University
Principal Investigator	Kawahito Koji 自治医科大学, 医学部, 教授 (90281740)
Co-Investigator(Kenkyū-buntansha)	坂元尚哉東京都立大学, システムデザイン研究科, 准教授 (20361115) 木村直行自治医科大学, 医学部, 教授 (20382898) 中村匡徳名古屋工業大学, 工学(系)研究科(研究院), 教授 (20448046) 相澤啓自治医科大学, 医学部, 教授 (50398517)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	大動脈二尖弁 / 壁剪断応力 / 共培養モデル
Outline of Final Research Achievements	We conducted an in vitro study using human aortic endothelial cells (EC)-smooth muscle cells (SMC) coculture model to investigate cellular interactions associated with blood vessel pathophysiology under WSS conditions. In this study, we newly constructed a coculture model with centrifugally compressed cell-collagen combined construct (C6), which withstands higher WSS conditions. The expression of a-smooth muscle actin (αSMA) in SMAs was significantly increased in the C6 coculture model exposed to WSS of 2 Pa compared with that of cells in the SMC monoculture model at 2 Pa and those in the C6 coculture model exposed to the 20 Pa condition. Similarly, WSS conditions of 2 and 20 Pa also induced different expression ratios of matrix metalloproteinases and their inhibitors in the C6 coculture model, but did not in monocultured ECs and SMCs. Our data suggested that WSS related-signaling transduced by ECs may lead to morphological and functional changes of SMCs.
Free Research Field	心臓血管外科
Academic Significance and Societal Importance of the Research Achievements	大動脈弁二尖弁は頻度の高い先天性心疾患で約半数で上行大動脈が拡大するが、その機序は十分に解明されていない。今回、大動脈血管内皮細胞と大動脈血管平滑筋細胞の単培養モデルも作成し、これらを対照群とした実験を行うことで、血行力学ストレスに曝露される環境下で血管内皮細胞によるsignal transductionを介し、血管平滑筋細胞における機能的・形態的変化が間接的に誘発される可能性が示された。大動脈二尖弁症例は、解離や破裂などの重篤な大動脈疾患の発生頻度が高いことが報告されているが、本研究成果は、治療成績向上につながる創薬および新規バイオマーカー開発につながる可能性を有する。