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Disturbed Laminar Blood Flow Causes Impaired Fibrinolysis and Endothelial Fibrin Deposition In Vivo
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2019 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 119, no 2, p. 223-233Article in journal (Refereed) Published
Abstract [en]

Endothelial expression of tissue-type plasminogen activator (t-PA) is crucial for maintaining an adequate endogenous fibrinolysis. It is unknown how endothelial t-PA expression and fibrinolysis are affected by blood flow in vivo. In this study, we investigated the impact of different blood flow profiles on endothelial t-PA expression and fibrinolysis in the arterial vasculature. Induction of disturbed laminar blood flow (D-flow) in the mouse carotid artery potently reduced endothelial t-PA messenger ribonucleic acid and protein expression, and caused fibrin deposition. En face immunohistochemistry demonstrated that arterial areas naturally exposed to D-flow had markedly lower endothelial t-PA levels than areas with sustained laminar blood flow (S-flow), and displayed pronounced fibrin deposition despite an intact endothelium. In t-PA and plasminogen-deficient mice, fibrin deposition did not extend into S-flow areas, indicating that areas of D-flow and S-flow differ, not only in fibrinolytic capacity, but also in coagulation. Furthermore, plasminogen accumulation was found at D-flow areas, and infusion of recombinant t-PA activated fibrinolysis and significantly reduced the fibrin deposits. In conclusion, D-flow potently impairs the fibrinolytic capacity and causes endothelial fibrin deposition in vivo. Our data also indicate that t-PA is the limiting factor for efficient fibrinolysis at the thrombosis-prone D-flow areas in the arterial vasculature.

Place, publisher, year, edition, pages
Georg Thieme Verlag KG, 2019. Vol. 119, no 2, p. 223-233
Keywords [en]
t-PA, artery, fluid shear, fibrinogen/fibrin
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:umu:diva-156885DOI: 10.1055/s-0038-1676638ISI: 000458811700006PubMedID: 30602198OAI: oai:DiVA.org:umu-156885DiVA, id: diva2:1295225
Available from: 2019-03-11 Created: 2019-03-11 Last updated: 2019-03-11Bibliographically approved

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Ny, Tor

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