Pathophysiological analysis of pulmonary hypertension regulated by Senescence Signalling

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08098
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Niigata University
• Principal Investigator: HOYANO Makoto 新潟大学, 医歯学総合病院, 助教 (40790283)
• Co-Investigator(Kenkyū-buntansha): 南野 徹 新潟大学, 医歯学系, 教授 (90328063)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 肺高血圧症

Outline of Final Research Achievements

We developed a mouse model of hypoxia-induced pulmonary hypertension (PH) and found significant reduction of p53 expression in the lungs.
Our in vitro experiments with metabolomic analyses and the Seahorse XF extracellular flux analyzer indicated that suppression of p53 expression in PASMCs led to upregulation of glycolysis and downregulation of mitochondrial respiration, suggesting a proliferative phenotype resembling that of cancer cells. It was previously shown that systemic genetic depletion of p53 in a murine PH model led to more severe lung manifestations.
Although certain results were reported in experiments using pulmonary hypertensive mice, research using human specimens did not proceed due to difficulties in conducting sufficient research activities as a result of retirement and transfer of the research team.

Free Research Field

Cardiology

Academic Significance and Societal Importance of the Research Achievements

肺高血圧症におけるp53の役割について解明を進めることができた。今後、ヒト検体を用いた研究により、肺高血圧の発症・進行の機序を解明し、肺高血圧症の予防・治療法の確立を目指したい。