ArticleArteriosclerosis, thrombosis, and vascular biology2016
Inhibition of Thrombin With PPACK-Nanoparticles Restores Disrupted Endothelial Barriers and Attenuates Thrombotic Risk in Experimental Atherosclerosis.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Engineered immune-driven theranostics for clinical cardiology.Military Medical Research · 2025Review
- Perfluorocarbon nanoemulsions in drug delivery: design, development, and manufacturing.Theranostics · 2025Review
- Oral Nanoformulations in Cardiovascular Medicine: Advances in Atherosclerosis Treatment.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Effective Prevention of Arterial Thrombosis with Albumin-Thrombin Inhibitor Conjugates.Molecular pharmaceutics · 2023Article
- Peptide-Based Nanoparticles for Systemic Extrahepatic Delivery of Therapeutic Nucleotides.International journal of molecular sciences · 2023Review
- Review
- Simultaneous Inhibition of Thrombosis and Inflammation Is Beneficial in Treating Acute Myocardial Infarction.International journal of molecular sciences · 2023Article
- Evolving Diagnostic and Management Advances in Coronary Heart Disease.Life (Basel, Switzerland) · 2023Review
- Theranostic Nanomedicines for the Treatment of Cardiovascular and Related Diseases: Current Strategies and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2022Review
- D-Amino Acids and D-Amino Acid-Containing Peptides: Potential Disease Biomarkers and Therapeutic Targets?Biomolecules · 2021Review
- Sustained local inhibition of thrombin preserves renal microarchitecture and function after onset of acute kidney injury.Nanomedicine : nanotechnology, biology, and medicine · 2021Article
- Recent Advances in the Development of Theranostic Nanoparticles for Cardiovascular Diseases.Nanotheranostics · 2021Review
- Synthetic high-density lipoproteins loaded with an antiplatelet drug for efficient inhibition of thrombosis in mice.Science advances · 2020Article
- Biomimetic fibrin-targeted and HNano today · 2020Article
- Thrombin, a Mediator of Coagulation, Inflammation, and Neurotoxicity at the Neurovascular Interface: Implications for Alzheimer's Disease.Frontiers in neuroscience · 2020Review
- Nanoparticle-Mediated Drug Delivery for the Treatment of Cardiovascular Diseases.International journal of nanomedicine · 2020Review
- Biodistribution of Nanostructured Lipid Carriers in Mice Atherosclerotic Model.Molecules (Basel, Switzerland) · 2019Article
- Nanoparticle Therapy for Vascular Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Research Progress of Angiogenesis in Atherosclerotic Plaque in Chinese Medicine and Western Medicine.Chinese journal of integrative medicine · 2018Review
- Reporting Sex and Sex Differences in Preclinical Studies.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveA role for thrombin in the pathogenesis of atherosclerosis has been suggested through clinical and experimental studies revealing a critical link between the coagulation system and inflammation. Although approved drugs for inhibition of thrombin and thrombin-related signaling have demonstrated efficacy, their clinical application to this end may be limited because of significant potential for bleeding side effects. Thus, we sought to implement a plaque-localizing nanoparticle-based approach to interdict thrombin-induced inflammation and hypercoagulability in atherosclerosis. APPROACH AND
resultsWe deployed a novel magnetic resonance spectroscopic method to quantify the severity of endothelial damage for correlation with traditional metrics of vessel procoagulant activity after dye-laser injury in fat-fed apolipoprotein E-null mice. We demonstrate that a 1-month course of treatment with antithrombin nanoparticles carrying the potent thrombin inhibitor PPACK (d-phenylalanyl-l-prolyl-l-arginyl chloromethylketone) nanoparticle (1) reduces the expression and secretion of proinflammatory and procoagulant molecules, (2) diminishes plaque procoagulant activity without the need for systemic anticoagulation, (3) rapidly restores disrupted vascular endothelial barriers, and (4) retards plaque progression in lesion-prone areas.
conclusionsThese observations illustrate the role of thrombin as a pleiotropic atherogenic molecule under conditions of hypercholesterolemia and suggest the utility of its inhibition with locally acting antithrombin nanoparticle therapeutics as a rapid-acting anti-inflammatory strategy in atherosclerosis to reduce thrombotic risk.
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Registered trials
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