敗血症臓器障害におけるVEGFとアンジオポエチンの研究：短期型βブロッカーの作用

• 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 (2021-2022); University of Tsukuba (2020)
• Principal Investigator: 河野 了 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
• Project Status: Granted (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: VEGF / アンジオポエチン / ランジオロール

Outline of Research at the Start

本プロジェクトはVEGFとアンジオポエチンの関連性、またランジオロールの効果を明らかにするため、in vivoの基礎研究から人間を対象とした臨床研究に至るまで広い範囲で研究を行う。
研究１：ラットはWistar ST、8~12週齢、250-300gを敗血症モデルに使用する。LPSは15mg/Kgを頸静脈より静脈注射する。
研究２:Tie2受容体ノックアウトマウスを使用し、LPSを投与し敗血症モデルとする。
臨床研究（研究３）：対象病院に入院した早期敗血症患者でありランジオロールを投与している患者を対象とし、血中VEGFとアンジオポエチンを評価する。

Outline of Annual Research Achievements

We completed 3 years of this research. With working on acute lung injury, we also did many experiments on LPS-induced myocardial dysfunction and liver injury. Morphologically, landiolol hydrochloride, an ultra-short-acting β-blocker, plays vital role in lessening LPS-induced cardiac and liver injury. We used male Wistar rats at 8 weeks of age and were administered with either saline or lipopolysaccharide (LPS) for three hours (3h), and some of the LPS-administered rats were continuously treated with landiolol for 3h, extending experiments for 6h and 10h. We have seen the changes in both circulatory and tissue TNF-α and IL-6 with alteration of level of angiopoietin-2 in heart and liver. These changes were accompanied an LPS-induced considerable alteration in cardiac and liver levels of VEGF with Pa02. Here we found that the treatment of LPS-administered rats with landiolol starting from 3h significantly stopped the progression of cardiac dysfunction and liver injury with marked normalization of angiopoietin-2. This treatment also considerably normalized blood gas parameters, and tissue VEGF levels. Collectively, our data indicate that landiolol treatment in LPS-administered rats plays an essential role in attenuating cardiac dysfunction and liver injury through modulation of angiopoietin-2 with concomitant VEGF signaling reversal.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

We are on the planned activities of the research with the target milestone. The current study is almost on the right track, both from the context of the timeline and the number of research activities scheduled to be done to properly manage the project budget and research facilities available for the three years. We did not face any technical difficulties. Although Covid has impacted many things, we were careful to perform every target of the project with excellent efficiency and impact. The model generation was successful. We could successfully treat LPS-administered sepsis rats with landiolol. We could have all reagents available to conduct the studies. Of note, all these experiments were based on time-course and dose-dependent studies. Thus the time point and the dose were validated in these years for the experimental setting.

Strategy for Future Research Activity

We are still continuing this work on in vitro cell culture and knockout mice. Also, we are working on kidney and brain.

Research Products

• [Int'l Joint Research] HDRCRP/Bogra Medical college(バングラデシュ)
• [Journal Article] Omicron Transmissibility, Severity, Vaccines, and Future Perspectives. (2022)
  • Author(s): Maqbool, A.; Jesmin, S.; Shimojo, N.
  • Journal Title: Microbiology & Infectious Disease Volume: 6(4) Pages: 1-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Community survey, knowledge and attitude of Bangladeshi people during the time of Omicron Variant emergence (2022)
  • Author(s): Jesmin, S.; Maqbool, A.; Rahman, M.A.; Sohael, F.; Matsuishi, Y.; Shima, T.; Shimojo, N.; Kawano, S.; Yamaguchi, N.; Moroi, M
  • Journal Title: International J Biomed Res Prac Volume: 2(2) Pages: 1-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Brief Look at Omicron Condition in Bangladesh: Dealing with another variant. (2022)
  • Author(s): Jesmin, S.; Matsuishi, Y.; Sohael, F.; Imtiaz, A.; Shimojo, N.; Shima, T.; Yamaguchi, N.; Rahman, A.; Maqbool, A.; Kawano, S.,Moroi, M.
  • Journal Title: Journal of Medical - Clinical Research & Reviews Volume: 6(8) Pages: 1-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Monkeypox and an Interesting Look at Changes in Epidemiology (2022)
  • Author(s): Jesmin Subrina、Rahman Md. Arifur、Sohael Farzana、Shimojo Nobutake、Yamaguchi Naoto、Kawano Satoru、Moroi Masao
  • Journal Title: Journal of Biomedical Research & Environmental Sciences Volume: 3 Issue: 8 Pages: 889-894
  • DOI: 10.37871/jbres1528
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Covid-19 Vaccination status in Bogura district in Bangladesh. (2022)
  • Author(s): Jesmin, S.; Maqbool, A.; Sohael, F.; Islam, M.M.; Matsuishi, Y.; Shima, T.; Shimojo, N.; Kawano, S.; Rahman, M.A.; Yamaguchi, N.; Moroi, M.
  • Journal Title: Journal of Biomedical Research & Environmental Sciences Volume: 3(5) Pages: 516-521
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] COVID-19 Community Survey, Knowledge, Attitude and Practice by Bangladeshi Population. (2022)
  • Author(s): Jesmin, S.; Maqbool, A.; Sohael, F.; Islam, M.M.; Matsuishi, Y.; Shima, T.; Shimojo, N.; Kawano, S.; Rahman, M.A.; Yamaguchi, N.; Moroi, M.
  • Journal Title: Journal of Biomedical Research & Environmental Sciences Volume: 3(4) Pages: 367-372
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Covid-19, Co-morbidities and its impact on prognosis in a tertiary care hospital of Bangladesh. (2022)
  • Author(s): Mamun, M.A.; Maqbool, A.; Sohael, F.; Rahman, M.A.; Islam, M.M.;Shima, T.; Shimojo, N.; Kawano, S.; Yamaguchi, N.; Moroi, M.; Jesmin, S.
  • Journal Title: Journal of Medical - Clinical Research & Reviews, Volume: 6(2) Pages: 1-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prevalence of Diabetes Mellitus Among Tuberculosis patients in Bangladesh. (2022)
  • Author(s): Mamun, M.A.; Maqbool, A.; Sohael, F.; Rahman, M.A.; Islam, M.M.;Shima, T.; Shimojo, N.; Kawano, S.; Yamaguchi, N.; Moroi, M.; Jesmin, S.
  • Journal Title: Journal of Diabetes and its Complications Volume: 6(1) Pages: 1-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Covid-19 Vaccination status in Bogura district in Bangladesh. (2022)
  • Author(s): Jesmin, S.; Maqbool, A.; Sohael, F.; Islam, M.M.; Matsuishi, Y.; Shima, T.; Shimojo, N.; Kawano, S.; Rahman, M.A.; Yamaguchi, N.; Masao, M
  • Journal Title: Journal of Biomedical Research & Environmental Sciences Volume: -
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Covid-19, Co-morbidities and its impact on prognosis in a tertiary care hospital of Bangladesh. (2022)
  • Author(s): Mamun, M.A.; Maqbool, A.; Sohael, F.; Rahman, M.A.; Islam, M.M.; Shima, T.; Shimojo, N.; Kawano, S.; Yamaguchi, N.; Masao, M.; Jesmin, S
  • Journal Title: Journal of Medical - Clinical Research & Reviews Volume: 6(2) Pages: 1-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Daily walking habit reduces fasting blood sugar level in newly diagnosed diabetic participants in rural Bangladesh (2021)
  • Author(s): Jesmin Subrina、Shima Takeru、Yamaguchi Naoto、Sohael Farzana、Maqbool Adil、Rahman Arifur、Moroi Masao、Shimojo Nobutake、Kawano Saturo、Watanabe Koichi、Takeda Fumi、Soya Hideaki
  • Journal Title: The Journal of Physical Fitness and Sports Medicine Volume: 10 Issue: 2 Pages: 85-97
  • DOI: 10.7600/jpfsm.10.85
  • NAID: 130007997346
  • ISSN: 2186-8123, 2186-8131
  • Year and Date: 2021-03-25
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prevalence of Metabolic Syndrome Components among EarlyAge onset Acute Coronary Syndrome Patients in Bangladesh. (2021)
  • Author(s): Jesmin, S.; Maqbool, A.; Sultana, S.N.; Sohael, F.; Islam, M.M.; Matsuishi, Y.; Shima, T.; Shimojo, N.; Kawano, S.; Rahman, M.A.; Yamaguchi, N.; and Moro, M
  • Journal Title: Cardiology & Vascular Research Volume: 5(4) Pages: 1-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of Selective Endothelin Receptor Antagonist on Vegf Signaling System in Diabetic Penis: A Possible Clinical Implication for Diabetes Induced Erectile Dysfunction (2021)
  • Author(s): Adil Maqbool, Subrina Jesmin, Chishimba N Mowa, Sayeeda Nusrat Sultana,Nobutake Shimojo, Yujiro Matsuishi, Takeru Shima, Naoto Yamaguchi, Takashi Miyauchi, Satoru Kawano, Takashi Miyauchi
  • Journal Title: Cardiology & Vascular Research Volume: 5 Pages: 1-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Role of angiogenesis in sepsis (2022)
  • Author(s): Jesmin S, Kawano S
  • Organizer: nvited by Shuvo Diagnostic Center, Bogra, Bangladesh
  • Int'l Joint Research / Invited
• [Presentation] Angiogenesis and sepsis: Therapeutic implication (2021)
  • Author(s): Jesmin S, Kawano S
  • Organizer: A special online conference arranged by HDRCRP
  • Int'l Joint Research / Invited
• [Presentation] Can sepsis complications be reversed? (2021)
  • Author(s): Jesmin S, Kawano S
  • Organizer: Invited by TMSS, Bogra, Bangladesh
  • Int'l Joint Research / Invited
• [Presentation] How do you deal with sepsis complications? (2021)
  • Author(s): Jesmin S, Kawano S
  • Organizer: rranged by Sonar Desh Clinic, Bogra, Bangladesh
  • Int'l Joint Research / Invited