Title
Progression of the prothrombotic state in aging Bmal1-deficient mice Progression of the prothrombotic state in aging Bmal1-deficient mice
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Dallas, Tex. ,
Subject
Human medicine
Source (journal)
Arteriosclerosis, thrombosis, and vascular biology / American Heart Association. - Dallas, Tex., 1995, currens
Volume/pages
31(2011) :11 , p. 2552-2559
ISSN
1079-5642
1524-4636
ISI
000296605400029
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Objective-: The goal of this study was to examine the functional relationship between aging endothelium and thrombogenicity in a mouse model of premature aging. Methods and Results-: Coagulation tests and factors, blood cell counts, aorta endothelial function, aorta gene expression, and FeCl3-induced thrombosis in mesenteric blood vessels were analyzed in 10- to 30-week-old brain and muscle ARNT-like protein-1 (Bmal1)-deficient (knockout [KO]) mice and wild-type littermates. Ten-week-old KO mice manifested shortened prothrombin times (9.7 versus 11.3 seconds in wild-type) and elevated plasma fibrinogen (264 versus 172 mg/dL). At 30 weeks, factor VII (198% versus 149%), and platelet counts (2049 versus 1354 K/[mu]L) were increased in KO mice. Gene deficiency reduced the vasoactive nitric oxide production at 10 and 30 weeks and tended to reduce and increase the protein expression of thrombomodulin and von Willebrand factor, respectively, with aging. Shortened venular and arteriolar occlusion times on FeCl3-induced injury in 10-week-old KO mice confirmed higher thrombogenicity, culminating in priapism, observed in 60% of 25- to 30-week-old KO males. Conclusion-: Endothelial dysfunction and a hypercoagulable state cause early arterial and venous thrombogenicity in Bmal1 KO mice. With aging, progressive endothelial dysfunction, rising platelet counts, and high factor VII further enhance thrombogenicity, provoking priapism.
E-info
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