Abstract 5542: Annexin A5 Reduces Inflammation Mediated Vascular Remodelling and Post-interventional Atherosclerosis and Improves Vascular Function in Hypercholesterolemic Mice
Annexin A5 is abundant in atherosclerotic plaques, has anti-thrombotic properties, and it may reduce ischaemia-reperfusion injury. We showed that annexin A5 could reduce neointima development in mouse models of vein graft restenosis and cuff induced neointima formation in hypercholesterolemic ApoE3*Leiden mice. These effects were associated to a reduction in vessel wall leucocytes, indicating an anti-inflammatory effect. Here we further investigated if annexin A5 possess anti-inflammatory properties, and can affect functional consequences of inflammation in the vessel wall.
Methods. Plasma cytokines were measured by multiplex immunoassay in hypercholesterolemic ApoE3*Leiden mice 28 days after the placement of a vein graft in the carotid artery. Mice were treated with 1 mg/kg bw of annexin A5 or placebo once daily by intraperitoneal injection. In a second experiment, ApoE(−/−) mice were given a western diet for 16 weeks, after which they were treated with annexin A5 or placebo for 3 days, as above. They were then anaesthetised (isoflurane) and a Samba Preclin pressure transducer was introduced into the aortic arch through a carotid artery. Endothelium mediated dilatation was induced by intraperitoneal injection of 3 μg metacholine.
Results. Plasma levels of G-CSF, IFN γ and MIP-1β/CCL4 were significantly reduced by annexin A5 28 days after surgery. Vein graft remodelling was reduced by 48±12% in the annexin A5 treated mice. In apoE(−/−) mice, diastolic and systolic blood pressure were not significantly different. Placebo treated mice responded to metacholine with a minor reduction in diastolic (−1 mmHg at 3 minutes after injection) and systolic blood pressure (−5 mmHg). In contrast, annexin A5 treated mice responded with a pronounced and more long-lasting reduction in diastolic (− 11 mmHg) and systolic (−22 mmHg) blood pressures, p < 0.05 for both pressures.
Conclusions. Annexin A5 has systemic anti-inflammatory properties, as shown by reduced plasma cytokine levels, as well as it (as previously shown) blocks vascular inflammation in disease models. It can also normalise disease related impairment of endothelium mediated dilatation. Annexin A5 may have therapeutic benefits in inflammation associated vascular disease.