2021 Fiscal Year Final Research Report

Demonstration and mechanism elucidation of the inhibition of aortic valve calcification by controlling expression of extracellular matrix protein

Research Project

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Project/Area Number	19K09089
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Hirosaki University
Principal Investigator	Seya Kazuhiko 弘前大学, 医学研究科, 助教 (40281919)
Co-Investigator(Kenkyū-buntansha)	于在強弘前大学, 医学研究科, 助教 (40624268) 福田幾夫弘前大学, 医学研究科, 名誉教授 (50344594) 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)	2019-04-01 – 2022-03-31
Keywords	大動脈弁狭窄症 / 異所性石灰化 / 大動脈弁間質細胞 / マトリックスGlaタンパク質 / テネイシンX
Outline of Final Research Achievements	In this study, we investigated the properties of human aortic valve interstitial cells (HAVICs) obtained from calcified aortic stenosis patients and of various signaling pathways involved in the ectopic calcification of HAVICs. In these investigations, we also measured the expression of extracellular matrix proteins. As a result, we found that the signaling pathway mediated by the bone morphogenetic protein (BMP2)-Smad1/5/8 transcription factor activated by the tumor necrosis factor (TNF-α) may be associated with the decreased expression of extracellular matrix proteins, such as matrix Gla protein (MGP) and tenascin X (TNX). In the future, we will molecular biologically clarify the relationship between the TNF-α-BMP2-Smad1/5/8 signaling pathway and the decreased expression of MGP/TNX genes and proteins.
Free Research Field	循環器薬理学
Academic Significance and Societal Importance of the Research Achievements	本研究では異所性石灰化について動脈硬化以外の要因、すなわち加齢変性に着目することにある。すなわち、標的タンパク質低発現細胞を特定し、この細胞を減らすことで病態軽減をめざしていく。異所性石灰化誘発機構の解明は、大動脈弁狭窄症の病態基盤を構築することになる。かつ石灰化シグナリング機構を抑制する活性物質に基づいた新規薬物治療薬の開発に貢献するところに創造性があり、その結果として高齢者の健康寿命向上に寄与できると考える。