2022 Fiscal Year Final Research Report

Does smooth muscle maturation, an indicator of plaque stabilization, also appear in the intima after drug-eluting stent placement?

Research Project

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Project/Area Number	20K07398
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 49020:Human pathology-related
Research Institution	Tokyo Women's Medical University (2022) Tokyo Medical University (2020-2021)
Principal Investigator	Kurata Atsushi 東京女子医科大学, 医学部, 教授 (10302689)
Co-Investigator(Kenkyū-buntansha)	黒田雅彦東京医科大学, 医学部, 主任教授 (80251304) 大野慎一郎東京医科大学, 医学部, 講師 (90513680)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	動脈硬化 / 冠動脈ステント / 平滑筋 / 免疫組織化学 / h-caldesmon / calponin / FAP / sirolimus
Outline of Final Research Achievements	We have proposed that intermediate differentiation of arterial intimal smooth muscle cells (SMCs) is an indicator of plaque stabilization. In the present study, we investigated whether intermediate differentiation of intimal SMCs is involved in the reduction of stent restenosis, especially with sirolimus drug-eluting stents. Increased h-caldesmon and calponin expression along with decreased FAP expression were used as indicators of intermediate differentiation. Immunohistochemical analysis of 20 post-stent autopsies and the addition of the drugs to cultured human coronary artery SMCs both revealed that sirolimus has a differentiating effect on SMCs. We propose that intermediate SMC differentiation is a common factor in both coronary plaque stabilization and prevention of stent restenosis.
Free Research Field	血管病理学
Academic Significance and Societal Importance of the Research Achievements	心筋梗塞等の動脈硬化性疾患の大部分はプラークの破綻から生じる。破綻しにくい安定プラークは、脂質コアが小さく、脂質コアを覆う、平滑筋を主成分とする線維性被膜が増大している。一方、ステント挿入後の議論では、平滑筋の増生がステント再狭窄に関わる悪玉とされている。このように平滑筋の量ではプラーク安定化とステント挿入後予後で矛盾した結果となる。が、本研究でsirolimus溶出ステントにて平滑筋が分化したことは、動脈内膜平滑筋の中間的分化がプラーク安定化の指標となるというこれまでの我々の提言と併せて、動脈内膜平滑筋の中間的分化が、冠動脈プラーク安定化とステント再狭窄予防の両者に共通した因子と提言できる。