Annexin A5 reduces early plaque formation in ApoE -/- mice

Annexin A5 (AnxA5) exerts anti-inflammatory, anticoagulant and anti-apoptotic effects through its binding to cell surface expressed phosphatidylserine. We previously showed that AnxA5 can stabilize advanced atherosclerotic plaques by reducing macrophage infiltration. We now investigated the effects of AnxA5 administration on the onset of atherosclerosis development. Eight-week-old ApoE-/- mice were fed a western diet while being administered AnxA5 or control (M1234) for a total of 6 weeks. AnxA5 administration reduced plaque size in the aortic root as well as the aortic arch by 36% and 55% respectively. As determined by immunohistochemistry, administration of AnxA5 further stabilized plaque by reducing macrophage content and increasing smooth muscle cell content. Furthermore, the pre-treatment of HUVEC's with AnxA5 reduced monocyte adhesion under flow-conditions. Finally, AnxA5 administration results in a trend to reduced cell death more pronounced in the aortic arch than the aortic root. In conclusion, treatment with AnxA5 before the onset of atherosclerosis reduces plaque formation in a murine model of atherosclerosis in part by reducing apoptotic rates further to its beneficial effect on macrophage infiltration and activation.