Journal article
ADAMTS13 modulates atherosclerotic plaque progression in mice via a VWF‐dependent mechanism
Journal of thrombosis and haemostasis, Vol.12(2), pp.255-260
02/2014
DOI: 10.1111/jth.12456
PMID: 24261607
Abstract
Summary
Background
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.
Objective
We generated triple knockout Adamts13−/−/Vwf−/−/ApoE−/− mice to determine whether ADAMTS13 modulates atherosclerosis through its proteolytic effects on VWF or other potential mechanisms.
Methods
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.
Results
Deficiency of VWF in Adamts13−/−/ApoE−/− mice (Adamts13−/−/Vwf−/−/ApoE−/−) completely reversed exacerbated atherosclerosis (P < 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 (P < 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.
Conclusions
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.
Details
- Title: Subtitle
- ADAMTS13 modulates atherosclerotic plaque progression in mice via a VWF‐dependent mechanism
- Creators
- C Gandhi - University of IowaA Ahmad - University of IowaK. M Wilson - University of IowaA. K Chauhan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of thrombosis and haemostasis, Vol.12(2), pp.255-260
- DOI
- 10.1111/jth.12456
- PMID
- 24261607
- NLM abbreviation
- J Thromb Haemost
- ISSN
- 1538-7933
- eISSN
- 1538-7836
- Number of pages
- 6
- Grant note
- American Heart Association (#7520015)
- Language
- English
- Date published
- 02/2014
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094405802771
Metrics
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