The Effect of Rosuvastatin on a murine model of deep vein thrombosis

Introduction: Rosuvastatin reduces C-reactive protein and cardiovascular mortality. After deep vein thrombosis (DVT), elevated inflammatory markers persist. We hypothesize that statins may reduce the inflammation that may be associated with the development of post thrombotic syndrome (PTS). Material...

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Main Authors: Megan E. Barney, Shenghao Zhou, Anh Le-Cook, Naly Setthavongsack, Gabriel Nager, Jennifer M. Loftis, Randy L. Woltjer, Monica Hinds, Khanh P. Nguyen
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Thrombosis Update
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666572725000033
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author Megan E. Barney
Shenghao Zhou
Anh Le-Cook
Naly Setthavongsack
Gabriel Nager
Jennifer M. Loftis
Randy L. Woltjer
Monica Hinds
Khanh P. Nguyen
author_facet Megan E. Barney
Shenghao Zhou
Anh Le-Cook
Naly Setthavongsack
Gabriel Nager
Jennifer M. Loftis
Randy L. Woltjer
Monica Hinds
Khanh P. Nguyen
author_sort Megan E. Barney
collection DOAJ
description Introduction: Rosuvastatin reduces C-reactive protein and cardiovascular mortality. After deep vein thrombosis (DVT), elevated inflammatory markers persist. We hypothesize that statins may reduce the inflammation that may be associated with the development of post thrombotic syndrome (PTS). Materials and methods: Wildtype CD1 mice were fed either regular chow or 1 mg/kg rosuvastatin diets for 1 week prior to surgically induced DVT. Thrombus weights, plasma inflammatory markers, and histology were examined on postoperative days 3 and 7. Results: Thrombus weights were equivalent in the rosuvastatin treated mice compared to control mice on day 3 (1.25 mg/g±0.61 vs 1.46 mg/g±0.61, p = 0.23) and day 7 (1.07 mg/g ± 0.39 vs 1.04 mg/g±0.32, p = 0.43). On day 3, rosuvastatin treated mice demonstrated decreased levels of monocyte chemoattractant protein-1(MCP-1) (8.20 pg/mL ± 4.07 vs 17.37 pg/mL ±3.26, p = 0.04) and tumor necrosis factor-α (TNF-α) (2.42 pg/mL ±0.42 vs 4.74 pg/mL ± 0.91, p = 0.02) in comparison to the control mice. On day 7, rosuvastatin treated mice demonstrated increased levels of interferon-γ (IFN-γ) (4.22 pg/mL ±5.02 vs 0.49 pg/mL ±0.01, p = 0.04) in comparison to the control mice. There was a significant increase in collagen deposition seen both in the thrombus (2.00 ± 0.63 vs 0.75 ± 0.46, p = 0.002) and vein wall (2.33 ± 0.82 vs 1.13 ± 0.35 p = 0.008) on day 7 in the rosuvastatin treated animals compared to the control animals. Conclusions: After DVT, rosuvastatin did not accelerate thrombus resolution nor did it affect thrombus formation. However, rosuvastatin decreases MCP-1 and TNF-α during thrombus formation and increases IFN-γ in early thrombus resolution. Additionally, rosuvastatin may promote positive remodeling within the thrombus but increases vein wall fibrosis.
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spelling doaj-art-8cc2956ada7f4e4ebff0217d6c1d35922025-02-12T05:32:55ZengElsevierThrombosis Update2666-57272025-03-0118100200The Effect of Rosuvastatin on a murine model of deep vein thrombosisMegan E. Barney0Shenghao Zhou1Anh Le-Cook2Naly Setthavongsack3Gabriel Nager4Jennifer M. Loftis5Randy L. Woltjer6Monica Hinds7Khanh P. Nguyen8Oregon Health and Sciences University, Portland, OR, USA; Corresponding author. 3181 SW Sam Jackson Park Road, OP11, 97239, Portland, OR, USA.Pacific Northwest University-Health Sciences, Yakima, WA, USAOregon Health and Sciences University, Portland, OR, USAVA Portland Healthcare System, Portland, OR, USAOregon Health and Sciences University, Portland, OR, USAOregon Health and Sciences University, Portland, OR, USA; VA Portland Healthcare System, Portland, OR, USAOregon Health and Sciences University, Portland, OR, USAOregon Health and Sciences University, Portland, OR, USAOregon Health and Sciences University, Portland, OR, USA; VA Portland Healthcare System, Portland, OR, USAIntroduction: Rosuvastatin reduces C-reactive protein and cardiovascular mortality. After deep vein thrombosis (DVT), elevated inflammatory markers persist. We hypothesize that statins may reduce the inflammation that may be associated with the development of post thrombotic syndrome (PTS). Materials and methods: Wildtype CD1 mice were fed either regular chow or 1 mg/kg rosuvastatin diets for 1 week prior to surgically induced DVT. Thrombus weights, plasma inflammatory markers, and histology were examined on postoperative days 3 and 7. Results: Thrombus weights were equivalent in the rosuvastatin treated mice compared to control mice on day 3 (1.25 mg/g±0.61 vs 1.46 mg/g±0.61, p = 0.23) and day 7 (1.07 mg/g ± 0.39 vs 1.04 mg/g±0.32, p = 0.43). On day 3, rosuvastatin treated mice demonstrated decreased levels of monocyte chemoattractant protein-1(MCP-1) (8.20 pg/mL ± 4.07 vs 17.37 pg/mL ±3.26, p = 0.04) and tumor necrosis factor-α (TNF-α) (2.42 pg/mL ±0.42 vs 4.74 pg/mL ± 0.91, p = 0.02) in comparison to the control mice. On day 7, rosuvastatin treated mice demonstrated increased levels of interferon-γ (IFN-γ) (4.22 pg/mL ±5.02 vs 0.49 pg/mL ±0.01, p = 0.04) in comparison to the control mice. There was a significant increase in collagen deposition seen both in the thrombus (2.00 ± 0.63 vs 0.75 ± 0.46, p = 0.002) and vein wall (2.33 ± 0.82 vs 1.13 ± 0.35 p = 0.008) on day 7 in the rosuvastatin treated animals compared to the control animals. Conclusions: After DVT, rosuvastatin did not accelerate thrombus resolution nor did it affect thrombus formation. However, rosuvastatin decreases MCP-1 and TNF-α during thrombus formation and increases IFN-γ in early thrombus resolution. Additionally, rosuvastatin may promote positive remodeling within the thrombus but increases vein wall fibrosis.http://www.sciencedirect.com/science/article/pii/S2666572725000033Deep vein thrombosisThrombus resolutionRosuvastatinIVC ligationMurine modelStatin
spellingShingle Megan E. Barney
Shenghao Zhou
Anh Le-Cook
Naly Setthavongsack
Gabriel Nager
Jennifer M. Loftis
Randy L. Woltjer
Monica Hinds
Khanh P. Nguyen
The Effect of Rosuvastatin on a murine model of deep vein thrombosis
Thrombosis Update
Deep vein thrombosis
Thrombus resolution
Rosuvastatin
IVC ligation
Murine model
Statin
title The Effect of Rosuvastatin on a murine model of deep vein thrombosis
title_full The Effect of Rosuvastatin on a murine model of deep vein thrombosis
title_fullStr The Effect of Rosuvastatin on a murine model of deep vein thrombosis
title_full_unstemmed The Effect of Rosuvastatin on a murine model of deep vein thrombosis
title_short The Effect of Rosuvastatin on a murine model of deep vein thrombosis
title_sort effect of rosuvastatin on a murine model of deep vein thrombosis
topic Deep vein thrombosis
Thrombus resolution
Rosuvastatin
IVC ligation
Murine model
Statin
url http://www.sciencedirect.com/science/article/pii/S2666572725000033
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