Role of Tissue-Type Plasminogen Activator in Remodeling of the Ductus Arteriosus

• Saito Junichi

  Cardiovascular Research Institute, School of Medicine, Yokohama City University Department of Cardiovascular Medicine, School of Medicine, Yale University

• Ishikawa Yoshihiro

  Cardiovascular Research Institute, School of Medicine, Yokohama City University

• Yokoyama Utako

  Cardiovascular Research Institute, School of Medicine, Yokohama City University Department of Physiology, School of Medicine, Tokyo Medical University

抄録

Vascular remodeling (e.g., intimal thickening) is necessary for complete closure of the ductus arteriosus (DA). Smooth muscle cells are reported to contribute to DA remodeling. In contrast, the contribution of endothelial cells remains largely unknown. Recent data showed that tissue-type plasminogen activator (t-PA) was highly expressed in the endothelial cells of rat and human DA. It is well known that t-PA is an activator of the blood fibrinolytic system, but t-PA-induced localized proteolysis has been reported to play an important role in vascular development. We found that t-PA-induced plasminogen-plasmin conversion promoted matrix metalloproteinase-2 activation in endothelial cells of rat DA. Gelatinase activity was noted at the internal elastic laminae (IEL) of rat and human DA on in situ gelatin zymography. The in vivo injection of plasminogen to pre-term rats increased gelatinase activation, IEL disruption, and the subsequent intimal thickening formation in the pre-term rat DA. Human DA results partly supported the rat DA findings, suggesting that t-PA-mediated DA remodeling may also be present in the human DA. Current pharmacotherapy for patent DA (PDA) mainly focuses on increasing vascular constriction. Elucidating the molecular mechanisms of DA remodeling may help to expand the range of therapeutic strategies for PDA.

収録刊行物

• Circulation Reports

  Circulation Reports 2 (4), 211-217, 2020-04-10

  一般社団法人 日本循環器学会

キーワード

• Ductus arteriosus
• Endothelial cell
• Internal elastic laminae
• Intimal thickening
• Tissue-type plasminogen activator

詳細情報

• CRID: 1390565134847266048
• NII論文ID: 130007830858
• DOI: 10.1253/circrep.cr-20-0015
• ISSN: 24340790
• Web Site: https://www.jstage.jst.go.jp/article/circrep/2/4/2_CR-20-0015/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2020371488
• 本文言語コード: en
• データソース種別:
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  • Crossref
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