Proteolysis of Von Willebrand Factor Influences Inflammatory Endothelial Activation and Vascular Compliance in Atherosclerosis
Koya Ozawa, Matthew Muller, Oleg Varlamov, Hagai Tavori, William Packwood, Paul Müeller, Aris Xie, Zaverio M. Ruggeri, Dominic W. Chung, José A. López, Jonathan R. Lindner
Abstract
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.