Elucidation of the onset mechanism of diabetic macroangiopathy via mtROS and Nrf2

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kumamoto University
• Principal Investigator: Kukidome Daisuke 熊本大学, 大学院生命科学研究部(医), 特定研究員 (10555759)
• Co-Investigator(Kenkyū-buntansha): 瀬ノ口 隆文 熊本大学, 大学院生命科学研究部(医), 特任講師 (00530320) ; 松村 剛 熊本大学, 大学院生命科学研究部(医), 准教授 (20398192)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 酸化ストレス / ミトコンドリア / 動脈硬化

Outline of Final Research Achievements

The aim of the present study was to investigate the effect of endotherial -specific mitochondrial reactive oxygen species(mtROS)reducty, and the involvement of NRF2 expression an atheroscrelotic lesion formation in apoE-deficient(apoE-/-)mice.　We detected the decrease in the arteriosclerosis lesion formation in endotherial cells in the aoltic sinus and the enface of aorta in high-fat diet fed endotheriales -specific MnSOD overexpressed apoE deficient (eMnSODtg apoE-/-) mice compared with a high-fat diet fed apoE-/- mice.　In in vitro assay, although high-glucose condition increase the mtROS in human aortic endotherial cells, that did not increase NRF2 expression.
These results suggested that overexpression of MnSOD in endotherial cells suppressed the atheroscrelotic lesion formation in high -fat fed apoE-/- mice without the suppression of NRF2 expression.

Free Research Field

糖尿病合併症

Academic Significance and Societal Importance of the Research Achievements

糖尿病大血管合併症は、糖尿病患者のQOLや健康寿命低下に多大な影響を及ぼすと考えられる。mtROSと動脈硬化発症の関連を明らかにすることは、糖尿病患者のQOLや健康寿命改善に寄与しうると考えられる。