Proteolysis of Von Willebrand Factor Influences Inflammatory Endothelial Activation and Vascular Compliance in Atherosclerosis

Koya Ozawa, Matthew A. Muller, Oleg Varlamov, Hagai Tavori, William Packwood, Paul A. Mueller, Aris Xie, Zaverio Ruggeri, Dominic Chung, José A. López, Jonathan R. Lindner

    Research output: Contribution to journalArticlepeer-review

    1 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)1017-1028
    Number of pages12
    JournalJACC: Basic to Translational Science
    Volume5
    Issue number10
    DOIs
    StatePublished - Oct 2020

    Keywords

    • atherosclerosis
    • molecular imaging
    • platelets
    • von Willebrand factor

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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