Statins Improve the Resolution of Established Murine Venous Thrombosis: Reductions in Thrombus Burden and Vein Wall Scarring

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Statins Improve the Resolution of Established Murine Venous Thrombosis: Reductions in Thrombus Burden and Vein Wall Scarring

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Title: Statins Improve the Resolution of Established Murine Venous Thrombosis: Reductions in Thrombus Burden and Vein Wall Scarring
Author: Kessinger, Chase W.; Kim, Jin Won; Henke, Peter K.; Thompson, Brian; McCarthy, Jason R.; Hara, Tetsuya; Sillesen, Martin; Margey, Ronan J. P.; Libby, Peter; Weissleder, Ralph; Lin, Charles P.; Jaffer, Farouc A.

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Citation: Kessinger, C. W., J. W. Kim, P. K. Henke, B. Thompson, J. R. McCarthy, T. Hara, M. Sillesen, et al. 2015. “Statins Improve the Resolution of Established Murine Venous Thrombosis: Reductions in Thrombus Burden and Vein Wall Scarring.” PLoS ONE 10 (2): e0116621. doi:10.1371/journal.pone.0116621. http://dx.doi.org/10.1371/journal.pone.0116621.
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Abstract: Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins—lipid-lowering agents with anti-thrombotic and anti-inflammatory properties—in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice). Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi) compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1), tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs), and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.
Published Version: doi:10.1371/journal.pone.0116621
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334538/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:14065560
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