Role of exosome in cellular communication of human saphenous vein wall- cross talk between fibroblasts and smooth muscle cells-

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18168
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Tatsukawa Takamitsu 旭川医科大学, 大学病院, 助教 (80837914)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 末梢動脈疾患 / 細胞外小胞 / 自家静脈グラフト狭窄

Outline of Final Research Achievements

To elucidate the mechanism of intima-media thickening of vein graft during distal arterial bypass surgery for peripheral arterial disease, we examined the existence of an extracellular vesicle (exosome)-mediated growth suppression mechanism between adventitia-derived fibroblasts (Fibs) and media-derived smooth muscle cells (SMCs).
Exosomes were extracted from culture supernatants of Fibs and SMCs derived from human great saphenous vein, and the effect of exosomes from Fibs on the proliferative potential of SMCs was confirmed. MicroRNAs(miRNA) in exosomes were analyzed by next-generation sequencing. As a result, we identified 45 miRNAs that were specifically up-regulated in Fibs-derived exosomes.

Free Research Field

血管外科

Academic Significance and Societal Importance of the Research Achievements

この研究の結果、エクソソームを介して平滑筋細胞の増殖を制御可能になった場合、末梢動脈バイパス術後の内膜中膜壁肥厚によるグラフト狭窄・閉塞という重大な合併症の頻度を減少させることが期待でき、治療予後、再治療介入率、患者のQOL、ひいては医療コストの改善につながると考えている。
現段階では、まだ細胞レベルでの結果段階ではあるが、候補遺伝子の同定、動物実験を経て、最終的には臨床へと、translatoinal researchとして進めるべき研究であると考えている。エクソソームの投与経路としては、血管内投与、薬剤コーティングバルーンによる局所塗布など検討されるが、検討が必要と考えている。