Role of dihydrofolate reductase in the regulation of endothelial function

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08238
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: University of the Ryukyus
• Principal Investigator: Noguchi Katsuhiko 琉球大学, 医学部, 非常勤講師 (70156181)
• Co-Investigator(Kenkyū-buntansha): 筒井 正人 琉球大学, 医学(系)研究科(研究院), 教授 (70309962)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 一酸化窒素 / 血管内皮細胞機能 / ジヒドロビオプテリン / テトラヒドロビオプテリン / ジヒドロ葉酸還元酵素 / 酸化ストレス

Outline of Final Research Achievements

An elevation of oxidized forms of tetrahydrobiopterin (BH4), especially dihydrobiopterin (BH2), has been reported in the setting of oxidative stress, such as atherosclerotic disorders, where eNOS is dysfunctional, but a role of dihydrofolate reductase (DHFR), an enzyme catalyzing intracellular conversion of BH2 to BH4, in the regulation of endothelial function in vivo remains to be clarified. To this end, we generated novel mice with endothelium-specific deficiency of Dhfr gene, endothelium-specific and temporal deficiency of the gene and with endothelium-specific expression of DHFR transgene, and we examined characteristics of phenotypes of these mice.

Free Research Field

循環器薬理学