Development of drugs focused on immune regulatory mechanisms that inhibit the onset and progression of aortic valve calcification

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16490
• 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): 2021-04-01 – 2023-03-31
• Keywords: 大動脈弁狭窄症 / PD-1/PD-L1 / 免疫チェックポイントタンパク / LPS

Outline of Final Research Achievements

We investigated the association between the presence of lipopolysaccharide (LPS), an indicator of Gram-negative bacteria, and PD-L1 expression, the presence of infiltration of CD8-positive T lymphocytes, CD163-positive macrophages, and FOXP3-positive regulatory T lymphocytes (Treg) in AS resection specimens and aortic valve calcification.
We observed significantly higher PD-L1 expression in LPS-detected cases. LPS was detected in tissues with strong valve calcification, but no coexistence between LPS and PD-L1 was observed in areas with poor calcification. In valve tissues where LPS was not detected, there was a high infiltration of CD163-positive macrophages and FOXP3-positive Tregs, consistent with the expression pattern of PD-L1 protein.

Free Research Field

Cardiovascular surgery

Academic Significance and Societal Importance of the Research Achievements

我々は、これまでの研究によって、大動脈弁狭窄症症例の石灰化した弁組織に、有意に免疫細胞と免疫チェックポイントタンパクが浸潤していることを明らかにした。このことから、大動脈弁の石灰化の発症・進行に免疫システムが大きく寄与している事が示唆されている。よって、さらに免疫システムとの関連を調べることにより、大動脈弁狭窄症の発症・進行を予防する治療薬ツール開発につながる重要な基礎データとなると考える。