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

Abstract

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.

Annexin Animal Models—From Fundamental Principles to Translational Research

“…In apoE −/− mice fed a western style diet, subsequent AnxA5 administration reduced recruitment and activation of monocytes to the inflamed lesion site, thereby reducing plaque inflammation [ 256 ]. Moreover, when AnxA5 was administered simultaneously with the western style diet, reduced apoptotic rates contributed to the significantly reduced plaque size [ 257 ]. Using hypercholesterolemic ApoE*3 Leiden mice as a model for MI-reperfusion injury, AnxA5 treatment strongly reduced infarct size and improved cardiac function, most likely via the attenuation of the post-ischaemic inflammatory response [ 258 ].…”

Long-circulating XTEN864-annexin A5 fusion protein for phosphatidylserine-related therapeutic applications

“…5 , 6 , S1). Stoer et al [ 27 ] and Burgmayer et al [ 26 ] demonstrated that anxA5 treatment reduced the amount of macrophages in different stages of plaque development, but attenuated plaque size and the amount of apoptotic cells only in early stages. The adventitia—the outer layer of the vessel wall—is a collagen-rich extracellular matrix with bunches of fibroblasts, perivascular nerves, and microvessels.…”

“…Besides its diagnostic and therapeutic potential in the important field of viral infection, anxA5 has shown promising therapeutic effects in several other areas as well. For cardiovascular disease, anxA5 was reported to reduce inflammation in advanced atherosclerotic plaques and to attenuate plaque progression in early disease [ 26 , 27 ]. Furthermore, anxA5 reduced vessel inflammation and atherosclerosis after arterial cuff placement or vein graft surgery [ 28 ].…”

Phosphatidylserine externalized on the colonic capillaries as a novel pharmacological target for IBD therapy

“…The cell adhesion assay was performed as described previously 25 . HUVECs were seeded to confluence in 6-well plates and then stimulated by LPS (0.2 μg/ml, Sigma) for 6 h. Then activated HUVECs were untreated or treated with ANXA5/A5m (250 nM) for 30 min in complete medium supplemented with 2.5 mM Ca 2+ , and labeled with Hoechst (Invitrogen, Carlsbad, CA).…”

“…In vivo ANXA5 dampens inflammation when administered to various mouse models 8 , 22 – 24 . Administration of ANXA5 reduces inflammation and suppresses plaque development in a PS-dependent manner 25 .…”