The role and mechanism of VEGFR2 on aortic valve calcification

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08813
• 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: Hirosaki University
• Principal Investigator: Yu Zaiqiang 弘前大学, 医学研究科, 助教 (40624268)
• Co-Investigator(Kenkyū-buntansha): 瀬谷 和彦 弘前大学, 医学研究科, 助教 (40281919) ; 大徳 和之 弘前大学, 医学研究科, 教授 (50374822) ; 今泉 忠淳 弘前大学, 医学研究科, 教授 (90232602)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 大動脈弁石灰化 / VEGFR2

Outline of Final Research Achievements

Although we recently demonstrated that human aortic valve interstitial cells (HAVICs) obtained from patients with AVS were highly sensitive to ectopic calcification stimulation, the cell types contributing to calcification are unknown. Most cultured P1 HAVICs were CD73-, CD90-, and CD105-positive, and CD34-negative. HAVICs were vascular endothelial growth factor receptor 2 (VEGFR2)-positive. Calcified aortic valve immunohistochemistry showed that all cells were positive for VEGFR2 and partly a-SMA. Further, VEGFR2-positive cells were more sensitive to tumor necrosis factor-a-induced ectopic calcification with or without a-SMA positivity. We conclude that HAVICs obtained from patients with AVS are VEGFR2- positive undifferentiated mesenchymal cells and may contribute to aortic valve ectopic calcification. Orengetokuto inhibited TNF-α induced calcification in vivo. we also corfirned that orengetokuto intake inhibited acceleration of aortic valve calcification of SHRs in vitro.

Free Research Field

心臓血管外科

Academic Significance and Societal Importance of the Research Achievements

我々は大動脈弁石灰化に関わる弁間質細胞の特徴を解明し、VEGFR2陽性の細胞は骨化誘導に対して反応し、石灰化刺激に対して反応性が高いことを明らかにした。大動脈弁石灰化の進行に対して抑制効果を持つ黄蓮解毒湯を発見した。これらの成果は今後大動脈弁石灰化のメカニズムの解明及び薬物治療の開発及び確立に対して意義が大きいと考えられる。