Elucidation of mechanisms under prothrombotic state with aging

2015 Fiscal Year Final Research Report

• Project/Area Number: 24591421
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Saitama Medical University (2015); Nagoya University (2012-2014)
• Principal Investigator: Yamamoto Koji 埼玉医科大学, 医学部, 教授 (90362251)
• Co-Investigator(Kenkyū-buntansha): KOJIMA Tetsuhito 名古屋大学, 医学部, 教授 (40161913)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 血栓症 / 老化 / ストレス / 炎症 / サイトカイン / 線溶 / 脂肪細胞 / PAI-1

Outline of Final Research Achievements

Elevated expression of plasminogen activator inhibitor-1 (PAI-1), a key molecule in developing thrombosis, was demonstrated in plasma and several tissues of a murine model of aging, e.g., 12-month-old or 24-month-old mice and klotho mutant (kl/kl) mice, in comparison with young mice. Renal glomerular fibrin deposition was also detected in aged mice and klotho mice, suggesting that aged mice are hypercoagulable due to the high expression of PAI-1. Endotoxin challenge and restraint stress induced PAI-1 gene expression together with renal fibrin deposition in a murine model of aging. High expression of PAI-1 mRNA corresponded to vascular endothelium and smooth muscle cells, hepatocytes, renal tubular epithelial cells, adrenomedullar cells, cardiomyocytes, and adipose cells in aged mice in respons to those stimuli. Thus, aged animals may be hyperresponsive to prothrombotic stimuli through the higher induction of PAI-1 gene compared to young counterparts.

Free Research Field

医歯薬学