2022 Fiscal Year Final Research Report

Patient specific assessment of hemodynamics by computational fluid dynamics in patients with chronic aortic dissection

Research Project

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Project/Area Number	18K08770
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	Kimura Naoyuki 自治医科大学, 医学部, 教授 (20382898)
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) 中村匡徳名古屋工業大学, 工学(系)研究科(研究院), 教授 (20448046) 伊藤智自治医科大学, 医学部, 講師 (30382881) 田中正史日本大学, 医学部, 教授 (80382927)
Project Period (FY)	2018-04-01 – 2023-03-31
Keywords	大動脈解離 / 剪断応力 / 数値流体力学計算 / 共培養モデル / 単培養モデル
Outline of Final Research Achievements	We investigated influence of hemodynamic stress on aortic enlargement in patients with aortic dissection (AD). Of acute type A AD patients who underwent surgery, we selected 6 who showed aortic growth (> 10 mm/year) and 5 who showed no aortic growth (< 3 mm/year). Wall shear stress (WSS) and wall pressure in false lumen were compared between the groups. Both groups showed WSS and wall pressure were highest at the mid-systolic, however, hemodynamic parameters were not different. Using a coculture model of endothelial cells (ECs) on collagen gels containing smooth muscle cells (SMCs) (non-AD model) and a monocultured SMCs model (false lumen model), we investigated influence of WSS on MMP expression in SMCs. Coculture model showed MMP-9 expression was increased as with WSS increase, and monocultured SMCs model showed MMP-2 expression was increased as with WSS increase, suggesting lack of interaction between ECs and SMCs may lead to different pathway promoting negative remodelling.
Free Research Field	心臓血管外科
Academic Significance and Societal Importance of the Research Achievements	A型解離術後の慢性大動脈解離を対象とした血流解析はこれまでなかった。本研究では大動脈非拡大群・拡大群の2群間で血行力学因子の発現に差を認めなかったが、人工血管置換後という要因が影響した可能性がある。in vitro 実験では、WSS依存性に平滑筋細胞からのMMP-2産生が増加しており、偽腔壁ではWSS直接負荷に応じ平滑筋細胞のphenotypeが変化し中膜組織の構造変化が進行する可能性が示唆された。今後も、大動脈解離に対する多角的な研究を継続して行い、臨床応用可能な新規の画像診断法やバイオマーカーの開発を目指す。また、安全で効果的な手術治療術式の確立のためにCFD解析を活用する予定である。