Author(s): Ewing MM, de Vries MR, Nordzell M, Pettersson K, de Boer HC,
Abstract Share this page
Abstract 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. CONCLUSIONS: 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.
This article was published in Arterioscler Thromb Vasc Biol
and referenced in Hereditary Genetics: Current Research