Stratification of coronary event risk using membrane type matrix metalloproteinase expression on peripheral blood mononuclear cell

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09426
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: University of Fukui
• Principal Investigator: UZUI HIROYASU 福井大学, 学術研究院医学系部門, 准教授 (50313763)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: プラーク破綻 / 細胞外マトリックス分解酵素

Outline of Final Research Achievements

Patients with type 2 diabetes were enrolled in this study. All subjects underwent computed tomography to analyze the plaque characteristics.Serum and circulating peripheral blood mononuclear cells (PBMNCs)were prepared from fasting blood sample.The prevalence of vulnerable plaque was 43% of subjects. MT1-MMP expression on PBMNCs in all patients with PPH was significantly elevated in cases compared to controls. In patients with vulnerable plaque, MT1-MMP expression was higher than that in without vulnerable plaque Furthermore, in multivariate analysis, increase of MT1-MMP expression on PBMNCs was independently related to the incidence of vulnerable plaque.The elevated MT1-MMP expression on PBMNCs is associated the existence of vulnerable plaque in type 2 diabetic patients with postprandial hyperglycemia. These finding suggested that the measurement of MT1-MMP on PBMNCs may become a new predictor of vulnerable plaque in postprandial hyperglycemia state.

Free Research Field

動脈硬化

Academic Significance and Societal Importance of the Research Achievements

心血管疾患発症メカニズムや、何をその発症のマーカーにするかは不明な点が多い。動脈硬化巣における細胞外マトリックス分解亢進が、直接プラークの脆弱化を生み、心血管イベント発症の要因の一つとされている。今回の研究において、細胞外マトリックスを分解する酵素（マトリックスメタロプロテアーゼ：MMPｓ）制御に関わる膜型MMP(MT-MMPs)発現に着目し、MT1-MMPの計測法を新しく見出し、動脈硬化病変との関連性を検討した。冠動脈イベント高リスクである食後高血糖患者に対しMT1-MMP発現と、不安定プラークの存在を評価し、MT1-MMP計測が冠動脈病変発症の予見予測に対し有用であることが明確になった。