Intravenous release of NO from lipidic microbubbles accelerates deep vein thrombosis resolution in a rat model
Abstract
Objective The experiment was designed to analyze whether and how nitric oxide (NO) microbubbles facilitates deep vein thrombosis (DVT) resolution in a rat model. Methods and results DVT was induced by ligation of the inferior vena cava (IVC) and left common iliac vein (LCIV) in a rat model. The rats were sacrificed at day 2 and day 8 after ligation. NO was wrapped in lipidic microbubbles which were injected (1.6ml/kg) via tail vein twice a day. Thrombi isolated from IVC were measured by weight (g) and weight length ratio (g/cm).The histological analysis of LCIV indicated that platelets and inflammatory cells aggregation were reduced. The expression of vascular cell adhesion molecule-1 (VCAM-1) was quantified by immunohistochemical (IHC) staining and western blot. The coagulation functions including prothrombin time (PT), thrombin time (TT),activated partial thromboplastin time (APTT) and fibrinogen (FIB) were tested as well.Vein walls from IVC were processed by real-time polymerase chain reaction (RT-PCR) for several endothelial genes including matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), thrombomodulin (TM), and endothelial nitric oxide synthase (eNOS). The thrombus weight and the expression of VCAM-1 significantly decreased after NO microbubbles treatment. The expression of these endothelial genes were significantly up-regulated by NO micribubbles. There was no statistical difference among the groups in terms of PT, APTT, and TT. Conclusion NO microbubbles significantly facilitate DVT resolution in a rat model. The antithrombotic properties of NO microbubbles may be associated with reduced platelets and inflammatory cells aggregation, enhanced collagen turnover and stimulus to an anticoagulant condition of endothelium.
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The in vitro stability of NO-loaded microbubbles is relatively low.
“Unfortunately, the in vitro stability of such NO-loaded microbubbles is relatively low.246”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [246]
Polymer or phospholipid shelled microbubbles have been developed to create a hydrophobic microenvironment for NO transportation and therapeutic delivery.
“Toward this goal, polymer192 or phospholipid246 shelled microbubbles have been developed in recent years to create a hydrophobic microenvironment for NO transportation and therapeutic delivery.”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [246]
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Nitric Oxide Insufficiency, Platelet Activation, and Arterial Thrombosis
Loscalzo, J. (2001) · Circulation Research · doi:10.1161/hh0801.089861 · Cited by 612 · see citing works
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Wo, Y., Brisbois, E. J., Bartlett, R. H., & Meyerhoff, M. E. (2016) · Biomaterials Science · doi:10.1039/c6bm00271d · Cited by 251 · see citing works
- Authors
- Wang, C., Yang, F., Xu, Z., Shi, D., Chen, D., Dai, J., Gu, N., & Jiang, Q.
- Affiliations
- Nanjing Drum Tower Hospital (CN)
- Southeast University (CN)
- Corresponding author
- Gu, Ning
- Jiang, Qing
- Venue
- Thrombosis Research
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 131
- Issue
- 1
- Pages
- e31-e38
- ISSN
- 0049-3848 (ISSN-L)
- OpenAlex
- W2039002545
- Cited by
- 28
- References
- 1
- Citations by year
- 2026: 3 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 1 · 2013: 2
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thrombosis Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81125013, 31000453)
- National Key Basic Research Program of China (2013CB733804)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Keywords
- nitric oxide, deep vein thrombosis, thrombus resolution, antithrombotic therapy, VCAM-1, platelet aggregation, endothelial nitric oxide synthase, matrix metalloproteinases, thrombomodulin, inferior vena cava ligation, coagulation function
- MeSH terms
- Animals, Disease Models, Animal, Drug Carriers, Fibrinogen, Fibrinolytic Agents, Gene Expression Regulation, Iliac Vein, Immunohistochemistry, Injections, Intravenous, Ligation, Lipids, Male, Nitric Oxide, Partial Thromboplastin Time, Prothrombin Time, RNA, Messenger, Thrombin Time, Time Factors, Vena Cava, Inferior, Blotting, Western, Rats, Sprague-Dawley, Thrombomodulin, Vascular Cell Adhesion Molecule-1, Venous Thrombosis, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Endothelial Cells, Microbubbles, Rats, Nitric Oxide Synthase Type III, Real-Time Polymerase Chain Reaction
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