• ADAMTS13 protein;
  • atherosclerosis;
  • inflammation;
  • neutrophils;
  • thrombosis;
  • von Willebrand Factor



ADAMTS13 reduces the adhesiveness of hyperactive ultra-large von Willebrand factor (ULVWF) multimers by cleaving them into smaller, less active multimers. Recently, we and others have demonstrated that ADAMTS13 reduces atherosclerosis in hypercholesteremic apolipoprotein E (ApoE−/−) deficient mice. It is not known whether ADAMTS13 modulates atherosclerosis directly or indirectly by cleaving ULVWF multimers.


We generated triple knockout Adamts13−/−/Vwf−/−/ApoE−/− mice to determine whether ADAMTS13 modulates atherosclerosis through its proteolytic effects on VWF or other potential mechanisms.


Female mice were fed a high-fat Western diet beginning at 6 weeks of age until they were sacrificed at 4 months. We compared the extent of atherosclerosis in the serial cross-sections of the aortic sinus using the Verhoeff-Van Gieson stain. Macrophage and neutrophil infiltration were quantified by immunohistochemistry. Under plain polarized light interstitial collagen content in the serial cross-sections of the aortic sinus was quantified using picrosirius red stain.


Deficiency of VWF in Adamts13−/−/ApoE−/− mice (Adamts13−/−/Vwf−/−/ApoE−/−) completely reversed exacerbated atherosclerosis (< 0.05 vs. Adamts13−/−/ApoE−/− mice). The lesion size, macrophage and neutrophil infiltration in the aortic sinus of Adamts13−/−/Vwf−/−/ApoE−/− mice were significantly decreased compared with Adamts13−/−/ApoE−/− mice (< 0.05), but similar to Vwf−/−/ApoE−/− mice. Additionally, interstitial collagen content in the aortic sinus of Adamts13//Vwf//ApoE−/− mice was significantly reduced compared with Adamts13−/−/ApoE−/− mice (P < 0.05), but similar to Vwf//ApoE−/− mice. Total cholesterol and triglyceride levels were similar among groups.


ADAMTS13 modulates inflammatory plaque progression in hypercholesterolemic mice through a VWF-dependent mechanism. These findings provide further evidence on the pathophysiological role for the ADAMTS13/VWF axis in atherosclerosis.