Lymphatic vessels acquires inflammatory abilities

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07336
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Okayama University of Science
• Principal Investigator: Ozaki Hiroshi 岡山理科大学, 獣医学部, 教授 (30134505)
• Co-Investigator(Kenkyū-buntansha): 水野 理介 岡山理科大学, 獣医学部, 教授 (30273080)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: リンパ管 / 血管 / 内皮細胞 / 平滑筋細胞 / 高血圧 / 炎症

Outline of Final Research Achievements

In this study, we aimed to examine if impaired lymphatic function may contribute to the pathogenesis of increasing blood pressure. In SHR lymphatic vessels, we found that endothelial activity of lymphatic vessels is functionally impaired with the development of increasing blood pressure, which is mediated through increased oxidative stress via the p38 MAPK/NADPH oxidase 2 pathway. These results suggest that the impaired lymphatic endothelial function may contribute to the pathogenesis of hypertension（Hypertension 2020）. We also found that Streptococcal streptolysin O causes vascular endothelial dysfunction and leads to increased blood pressure, which is mediated by PKCbeta-induced phosphorylation of the eNOS inhibitory site through TLR4 interaction. These results suggest that streptolysin O/TLR4/PKCbeta signaling may be a novel risk factor for the development of hypertension（J Pharmacol Exp Ther 2021）.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

現在、リンパ管の機能が高血圧病態にどの様に関わるかは明らかにされていない。本研究は、リンパ管内皮細胞の機能異常が高血圧モデルで見られることを示した最初のレポートである。一方、高血圧症で見られる腸内フローラなど常在細菌の乱れが生体に及ぼす影響は、未だ明らかにされていない。本研究は、高血圧で増加するStreptococcus属の菌体毒素が血管収縮障害を引き起こす可能性を示唆したもので、高血圧病態の解明に向けた端緒となる。