VEGF and angiopoietins in septic organ damage: action of short-term beta blockers

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09282
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Ibaraki Prefectural University of Health Science (2021-2023); University of Tsukuba (2020)
• Principal Investigator: Kawano Saotoru 茨城県立医療大学, 付属病院, 教授 (90323295)
• Co-Investigator(Kenkyū-buntansha): 下條 信威 筑波大学, 医学医療系, 講師 (20462210)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: VEGF / アンジオポエチン / ランジオロール

Outline of Final Research Achievements

In this research, we investigated the effects of landiolol on sepsis-induced multiple organ dysfunctions. Landiolol hydrochloride, an ultra-short-acting β-blocker, significantly reduces heart, lung, kidney, and liver injuries caused by lipopolysaccharide (LPS). We used 8-week-old male Wistar rats, administering either saline or LPS for three hours. Some LPS-administered rats were then treated with landiolol for an additional three hours, extending the experiments to six and ten hours.We observed changes in TNF-α, IL-6, angiopoietin-2 levels, and VEGF signaling. Starting landiolol treatment three hours after LPS administration significantly halted organ damage progression and normalized angiopoietin-2, blood gas parameters, and VEGF levels.Our findings suggest that landiolol is crucial for reducing organ damage in LPS-administered rats by modulating angiopoietin-2 and reversing VEGF signaling, offering a promising approach for sepsis-induced organ dysfunction.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究の社会的意義は、敗血症による多臓器不全（MODS）の新たな治療法を示した点にある。特に、ランジオロールがアンジオポエチン-2とVEGFシグナルを調節し、臓器損傷を軽減する効果を明らかにした。これにより、敗血症に伴う臓器不全の進行を遅らせ、患者の生存率向上に寄与する可能性がある。現在の臨床治療では十分でない部分に新たな治療オプションを提供し、特異的選択性のあるβ1ブロッカーが臨床現場で使用可能な有効な治療法となることを示唆している。