This study used in vivo molecular imaging to characterize endotheliall activation attributable to von Willebrand factor (vWF)-mediated platelet adhesion in atherosclerosis. In atherosclerotic mice lacking the low-density lipoprotein receptor on Western diet, the additional genetic deletion of the ADAMTS13, which cleaves endothelial-associated vWF, produced greater aortic molecular imaging signal for not only vWF and platelets, but also for endothelial adhesion molecules VCAM1 and P-selectin, larger plaque size, and lower aortic distensibility. Sustained ADAMTS13 therapy reduced signal for all 4 molecular targets and plaque size. We conclude that excess endothelial-associated vWF contributes to not only platelet adhesion, but also to up-regulation of endothelial cell adhesion molecules.
Keywords: AD13−/−, deficient for ADAMTS13; Apo-E−/−, deficient for apolipoprotein-E; BP, blood pressure; GPIbα, glycoprotein-Ibα; LDL, low-density lipoprotein; LDL-R, low-density lipoprotein receptor; LDL-R−/−, deficient for low-density lipoprotein receptor; MB, microbubble; NFκB, nuclear factor κ-light-chain-enhancer of activated B cells; WSD, Western-style diet; atherosclerosis; molecular imaging; platelets; vWF, von Willebrand factor; von Willebrand factor.
© 2020 The Authors.