Cited 55 times since 2010 (3.8 per year) source: EuropePMC Arteriosclerosis, thrombosis, and vascular biology, Volume 31, Issue 1, 14 2 2010, Pages 95-101 Annexin A5 therapy attenuates vascular inflammation and remodeling and improves endothelial function in mice. Ewing MM, de Vries MR, Nordzell M, Pettersson K, de Boer HC, van Zonneveld AJ, Frostegård J, Jukema JW, Quax PH
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.
