Role of Tissue-Type Plasminogen Activator in Remodeling of the Ductus Arteriosus.
Ductus arteriosus
Endothelial cell
Internal elastic laminae
Intimal thickening
Tissue-type plasminogen activator
Journal
Circulation reports
ISSN: 2434-0790
Titre abrégé: Circ Rep
Pays: Japan
ID NLM: 101746642
Informations de publication
Date de publication:
28 Mar 2020
28 Mar 2020
Historique:
entrez:
11
3
2021
pubmed:
12
3
2021
medline:
12
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33693232
doi: 10.1253/circrep.CR-20-0015
pmc: PMC7921361
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
211-217Informations de copyright
Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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