Annexin A5 Therapy Attenuates Vascular Inflammation and Remodeling and Improves Endothelial Function in Mice
| Autor: | Knut Pettersson, Margreet R. de Vries, Anton Jan van Zonneveld, M. Nordzell, Paul H.A. Quax, Hetty C. de Boer, Johan Frostegård, J. Wouter Jukema, M.M. Ewing |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Time Factors Endothelium Hypercholesterolemia Anti-Inflammatory Agents Inflammation Nitric Oxide Systemic inflammation Veins Mice Apolipoproteins E Internal medicine Cell Adhesion medicine Animals Annexin A5 Cells Cultured Vascular Patency Mice Knockout Vascular disease business.industry Monocyte Graft Occlusion Vascular Atherosclerosis medicine.disease Mice Mutant Strains Vasodilation Endothelial stem cell Chemotaxis Leukocyte Disease Models Animal Endocrinology medicine.anatomical_structure atherosclerosis restenosis annexin A5 inflammation vein grafting transgenic mice accelerated atherosclerosis vein grafts inhibition disease cells atherothrombosis mechanisms prevention placement Mutation Immunology Cytokines Tumor necrosis factor alpha Endothelium Vascular Inflammation Mediators medicine.symptom Cardiology and Cardiovascular Medicine business Injections Intraperitoneal |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology, 31(1), 95 Arteriosclerosis, Thrombosis, and Vascular Biology |
| Popis: | Objective— Annexin A5 (AnxA5) has antithrombotic, antiapoptotic, and antiinflammatory properties; we investigated its effectiveness against vascular inflammation, remodeling, and dysfunction in accelerated atherosclerosis. Methods and Results— AnxA5 (1 mg/kg per day or vehicle) was investigated in vascular injury models in hypercholesterolemic apolipoprotein E (ApoE)3*Leiden mice. AnxA5 treatment reduced adhesion and infiltration of leukocytes by 71% to 69% ( P =0.015, P =0.031) and macrophages by 51% to 87% ( P =0.014, P =0.018), as well as monocyte chemotactic protein-1 and tumor necrosis factor-α expression in a femoral artery inflammation model (perivascular cuff for 3 days), indicating reduced vascular inflammation. In a vein graft model, 28 days of AnxA5 treatment reduced vein graft thickening (48%; P =0.006) and leukocyte infiltration (46%; P =0.003). In these mice, reduced plasma concentrations of IFN-γ (−72%; P =0.040), granulocyte colony–stimulating factor (−41%; P =0.010), and macrophage inflammatory protein-1β (MIP-1β) (−66%; P =0.020) were measured, indicating reduced systemic inflammation. An in vitro endothelial cell model shows the importance of AnxA5's anticoagulant properties in reducing vascular inflammation. Endothelium-mediated dilatation in hypercholesterolemic ApoE (−/−) mice was improved by 3 days of AnxA5 treatment, shown by improved systolic and diastolic blood pressure reductions in response to metacholine, which could be abolished by l -Nitro-Arginine-Methyl Ester ( l -NAME), indicating nitric oxide involvement. Conclusion— AnxA5 reduced local vascular and systemic inflammation and vascular remodeling and improved vascular function, indicating that it has a therapeutic potential against atherosclerotic cardiovascular diseases. |
| Databáze: | OpenAIRE |
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