Investigate mechanism of endothelial dysfunction during SARS-CoV-2 infection

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20757
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Nguyen Cong Thanh 滋賀医科大学, 医学部, 特任助教 (80910489)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: CD38 / SARS-CoV-2 / Interleukin 6 / NAD / endothelial dysfunction / LDH-A / NMNAT

Outline of Final Research Achievements

This research aimed to define the role of CD38 expression on activated endothelial cells during SARS-CoV-2 infection. As result, in contrast to our first hypothesis of detrimental role of CD38, we found that CD38 expression played a vital role in regulating endothelial activation, inflammatory cytokine production, hypoxic response, protecting endothelial cells from stimulation by interleukin-6 and SARS-CoV-2 infection. In addition, activated endothelial cells in SARS-CoV-2-infected macaques showed an increased expression of CD38 together with lactate dehydrogenase A (LDH-A), but not nicotinamide mononucleotide adenylyl-transferase (NMNAT), suggesting that NAD consumption by CD38 could be rather compensated by hypoxic response than NAD biosynthesis pathways.

Free Research Field

Immunity

Academic Significance and Societal Importance of the Research Achievements

本研究により、活性化した内皮細胞におけるCD38の発現と役割が明らかになり、COVID-19における内皮機能障害のメカニズム解明に貢献することができた。その結果、感染症におけるCD38への介入の危険性が示唆された。 また、低酸素反応とNAD生合成経路を同時に標的とすることで、細胞内のNAD濃度を最適化し、内皮機能障害の軽減に貢献する可能性がある。