Development of novel aortic dissection model based on vascular endothelial dysfunction and elucidation of pathophysiological mechanisms

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: The University of Tokushima
• Principal Investigator: ISHIZAWA Keisuke 徳島大学, 大学院医歯薬学研究部(医学系), 教授 (60398013)
• Co-Investigator(Kenkyū-buntansha): 石澤 有紀 徳島大学, 大学院医歯薬学研究部(医学系), 講師 (40610192)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 動脈硬化 / 大動脈解離 / 血管内皮

Outline of Final Research Achievements

In the present study, we have succeeded to establish a novel acute aortic dissection model mouse. Aortic dissection in C57Bl/6J mouse is induced by the combined usage of Nω-nitro-L-arginine methyl ester (L-NAME), angiotensin II (Ang II), and β-aminopropionitrile (BAPN). L-NAME induces endothelial cell damage. Administration of Ang II elevated systolic blood pressure. BAPN is one of the lysyloxidase inhibitor, which causes vessel medial fragility. We named this model “LAB” model. Pitavastatin, an HMG-CoA inhibitor used as lipid lowering agent, suppressed the incidence of aortic dissection. From the results of in vitro analysis using cultured human umbilical vein endothelial cells, pitavastatin effects are mediated by extracellular signal-regulated kinase 5 (ERK5) activation. Our findings suggested that this novel “LAB” model are useful to examine the pathophysiology of aortic dissection and the estimation of the drug efficacy against aortic dissection.

Free Research Field

薬理学