Inflammatory and immune checkpoint markers are associated with the calcification of aortic valve

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18171
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Gunma University
• Principal Investigator: Tatsuishi Wataru 群馬大学, 医学部附属病院, 助教 (50722378)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: PD-1/PD-L1タンパク / 免疫チェックポイントタンパク / 大動脈弁石灰化

Outline of Final Research Achievements

In relation to Aortic stenosis, the purpose of this study was to elucidate the relationships among factors such as expression of programmed cell death-1 ligand (PD-L1), clinicopathologic characteristics, infiltrating immune cells, and disease severity.
PD-L1 expression in resected AVs was significantly associated with being nonsmoker, valve calcification, and the infiltration of CD8-positive T cells and CD163-positive macrophages. Disease severity and valve calcification were significantly associated with low infiltration of FOXP3-positive Tregs and high infiltration of CD8-positive T cells and CD163-positive macrophages. Moreover, calcified AVs with high PD-L1 expression showed active inflammation without FOXP3-positive Tregs but with high levels of CD8-positive T lymphocytes and CD163-positive macrophages.
Immune cell infiltration in the AVs and expression of the immune checkpoint protein PD-L1 were associated with the calcification of AS and disease severity.

Free Research Field

心臓血管外科

Academic Significance and Societal Importance of the Research Achievements

大動脈弁狭窄症において、大動脈弁の石灰化が存在する部位には免疫細胞浸潤と免疫チェックポイントタンパクの発現も強くなっていたという結果が得られた。このことから、大動脈弁石灰化に免疫チェックポイントタンパクが影響している可能性が示唆された。この制御因子を解明することで、今後の大動脈弁狭窄進行を抑制・治療することができる新たな薬剤が開発される可能性が見いだせた。