The role of NAD metabolites in progression of arteriosclerosis in chronic kidney disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08712
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Shimane University (2022); Keio University (2019-2021)
• Principal Investigator: KANDA TAKESHI 島根大学, 学術研究院医学・看護学系, 教授 (80317114)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 慢性腎臓病 / 動脈硬化 / NAD代謝

Outline of Final Research Achievements

Elevated blood levels of homocysteine (Hcy), an intermediate metabolite of methionine metabolism, are one of the risk factors for cardiovascular events in chronic kidney disease. In addition, it has been reported that alteration of NAD metabolites is involved in the development of lifestyle-related diseases such as obesity and diabetes. It has been suggested that nicotinamide-N-methyltransferase (NNMT), which catalyzes NAD and methionine metabolism, is a factor that regulates blood levels of Hcy. In this study, NNMT-overexpressing mice shows markedly increased blood levels of Hcy, but NNMT-deficient mice had no effect on Hcy production.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病の心血管イベントの抑制には高血圧、脂質異常症、糖尿病などの古典的危険因子やCa・Pの管理が重要であり、これまでのところ特異的な治療法は存在しない。現在NNMTの阻害薬の開発が進められ、NAD基質であるNMN・NAM投与の治験が行われており、本研究により基礎的なデータを提示することが可能となった。