Mechanism of GLP 1 / DDP4 in stress vascular disease and its therapeutic application

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04802
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Nagoya University
• Principal Investigator: Cheng XianWU 名古屋大学, 未来社会創造機構(医), 特任准教授 (30378228)
• Co-Investigator(Kenkyū-buntansha): 佐々木 健 浜松医科大学, 大学院医学系研究科, 技術専門職員 (20397433) ; 菊地 良介 名古屋大学, 医学部附属病院, 臨床検査技師 (30721435) ; 坂東 泰子 (暮石泰子) 名古屋大学, 医学部附属病院, 講師 (60452190) ; 竹下 享典 名古屋大学, 医学部附属病院, 准教授 (70444403)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 心理的ストレス / 血管新生 / 血管病 / ジペプチジルペプチダーゼ‐4

Outline of Final Research Achievements

Exposure to psychosocial stress is a risk factor for cardiovascular disease. Here, we have used dipeptidyl peptidase-4 (DPP4)-deficient mice and its inhibitor as well as glucagon-like peptide-1 (GLP-1) receptor agonist to explore the role of DPP4/GLP-1 axis in ischemia-induced neovascularization and diet-induced atherosclerosis. We demonstrated that stress impaired the recovery of the ischemic/normal blood-flow ratio throughout the follow-up period and capillary formation; and these changes DPP4 inhibition and GLP-1R activation improved these changes; these benefits were abrogated by adiponectin blocking and genetic depletion. Similarly, chronic stress accelerated diet-induced atherosclerotic lesion formation; and this effect was reversed by DPP4 inhibition. Our findings suggest that CatK might be a new therapeutic target for the chronic psychological stress-related neovascularization and cardiovascular diseases.

Free Research Field

老年医学