The role of PAR2 and autophagy in CKD-related atherosclerosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15993
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tohoku University
• Principal Investigator: Oe Yuji 東北大学, 東北メディカル・メガバンク機構, 助教 (00791980)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 血液凝固 / 血管石灰化 / ウレミックトキシン / 酸化ストレス / 炎症

Outline of Final Research Achievements

The aim of this study was to clarify the roles of coagulation factors and protease-activated receptor 2 (PAR2) in chronic kidney disease-related atherosclerosis, and the analysis was conducted using animal models. We combined adenine-induced nephropathy with a high phosphorus diet and found no changes in aortic calcification, inflammatory cytokines or autophagy markers due to PAR2 deficiency. Endothelial damage increases coagulation abnormality. To create a model of severe vascular calcification with a background of endothelial dysfunction, endothelial nitric oxide synthase deficient (eNOS) mice were fed with an adenine plus high phosphorus diet. eNOS deficiency exacerbated calcium deposition in the aorta and kidney, which was associated with inflammation, coagulation, and oxidative stress.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

当初予定していた実験ツールでは、血液凝固やPAR2が動脈硬化に与える影響を証明できなかったが、内皮障害を背景に血管石灰化や凝固や炎症が増悪する実験モデルを新たに構築した。今後このモデルを応用して、血液凝固関連因子やPAR, Autophagyの役割を検討することを予定している。