Abstract Number: PB0157
Meeting: ISTH 2020 Congress
Background: Von Willebrand factor (VWF) is a prothrombotic endothelial specific protein and unregulated elevated VWF levels present a risk factor for thrombus formation. Aging process has been associated with increased circulating levels of VWF.
1) To Explore the regulation of VWF expression during aging.
2) To determine association of increased VWF expression with thrombogenicity during aging.
3) To determine the molecular mechanism of aged-related upregulation of VWF expression.
Methods: Elisa, Western blot and RT-PCR analyses were used to determine circulating plasma, cellular protein, and mRNA levels of VWF in young and aged mice. Immunofluorescent analyses of major organs were performed to establish vascular pattern of VWF and the presence of platelet aggregates. Cultured endothelial cells were used as an in vitro model of aging to explore the mechanism of increased VWF levels.
Results: Increased plasma levels of VWF were observed in aged mice. VWF mRNA and protein levels were significantly increased in the brains, lungs, and livers, but not in kidneys and hearts of aged mice. In organs of aged mice that demonstrated increased VWF, the distribution pattern of expression was altered from primarily large vessels to include VWF detection in small vessels as well. Increased platelets aggregate formation in vessels of aged organs were concomitant with increased VWF expression. Aspirin treatment notably reduced platelets aggregates formation in the brain vasculature of aged mice. The prolonged culture of endothelial cells exhibited cell senescence that correlated with a significant increase in VWF mRNA. Increased VWF expression was specifically detected in senescent cell population.
Conclusions: VWF levels and expression patterns are significantly increased in response to aging in an organ-specific manner, which is concomitant with increased platelet aggregates formation as a risk factor for age-associated cardiovascular disorders. A potential mechanism of age-associated increase in VWF expression may be through cell senescence.
To cite this abstract in AMA style:Alavi P, Yousef Abdualla R, Bourque S, Nagendran J, Jahroudi N. von Willebrand Factor Levels and Expression Pattern Are Altered in Response to Aging [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/von-willebrand-factor-levels-and-expression-pattern-are-altered-in-response-to-aging/. Accessed December 5, 2021.
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