Search for unknown endogenous NOD1 ligands acting in the early stage of atherosclerosis

• Project/Area Number: 16K19651
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kyushu University
• Principal Investigator: KANNO SHUNSUKE 九州大学, 大学病院, 助教 (60725919)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: NOD1 / 動脈硬化 / 自然免疫 / 無菌マウス / Floch法 / 突然死 / Folch法 / 小児免疫

Outline of Final Research Achievements

Nucleotide-binding oligomerization domain (NOD)-1, which is an innate immune receptor recognizing bacterial peptidoglycan fragments, contributes to the development of atherosclerosis from early stage. Under germ-free condition, we analyzed the effect of Nod1 deficiency on the development of atherosclerosis in Apoe-/- mice. Nod1 deficiency resulted in reduced development of atherosclerotic lesions in Apoe-/- mice even without a microbiota. This result suggests the contribution of endogenous Nod1 ligands to the development of atherosclerosis. But we failed to determine the NOD1-stimulatory activity of mice atherosclerotic plaque by a bioassay using NOD1-expressing HEK293 cells, suggesting that the Nod1-stimulatory activity of Apoe-/- mice plaque might be very low.