Key result
Elderly porcine aortic valves exhibited lower expression of VWF, TFPI, and tPA, but higher levels of PAI-1 compared to young valves, demonstrating age-related changes in hemostatic protein regulation.
Hemostatic protein regulation in aortic valves changes with age, and proteins like VWF may promote calcific nodule formation in valvular interstitial cells, suggesting a role in calcific aortic valve disease.
Age may alter valvular endothelial hemostasis; leaves open its role in valve thrombosis or degeneration.
OBJECTIVE: Although valvular endothelial cells have unique responses compared with vascular endothelial cells, valvular regulation of hemostasis is not well-understood. Heart valves remodel throughout a person's lifetime, resulting in changes in extracellular matrix composition and tissue mechanical properties that may affect valvular endothelial cell hemostatic function. This work assessed valvular endothelial cell regulation of hemostasis in situ and in vitro as a function of specimen age. APPROACH AND RESULTS: Porcine aortic valves were assigned to 1 of 3 age groups: Young (YNG) (6 weeks); Adult (ADT) (6 months); or Elderly (OLD) (2 years). Histological examination of valves showed that secreted thrombotic/antithrombotic proteins localize at the valve endothelium and tissue interior. Gene expression and immunostains for von Willebrand factor (VWF), tissue factor pathway inhibitor, and tissue plasminogen activator in YNG porcine aortic valve endothelial cells were higher than they were for OLD, whereas plasminogen activator inhibitor 1 levels in OLD were higher than those for YNG and ADT. Histamine-stimulated YNG porcine aortic valve endothelial cells released higher concentrations of VWF proteins than OLD, and the fractions of VWF-140 fragments was not different between age groups. A calcific aortic valve disease in vitro model using valvular interstitial cells confirmed that VWF in culture significantly increased valvular interstitial cell nodule formation and calcification. CONCLUSIONS: Hemostatic protein regulation in aortic valve tissues and in valvular endothelial cells changes with age. The presence of VWF and other potential hemostatic proteins increase valvular interstitial cell calcification in vitro. Therefore, the increased capacity of elderly valves to sequester the hemostatic proteins, together with age-associated loss of extracellular matrix organization, warrants investigation into potential role of these proteins in the formation of calcific nodules.
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Balaoing et al. (2013) studied Calcific aortic valve disease. Specimen age (Elderly) vs. Young (6 weeks) and Adult (6 months) porcine valves was evaluated on Gene expression and immunostains for hemostatic proteins (VWF, TFPI, tPA, PAI-1). Elderly porcine aortic valves exhibited lower expression of VWF, TFPI, and tPA, but higher levels of PAI-1 compared to young valves, demonstrating age-related changes in hemostatic protein regulation.
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