Reduced acute vascular injury and atherosclerosis in hyperlipidemic mice transgenic for lysozyme

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Abstract

Hyperlipidemia promotes oxidant stress, inflammation, and atherogenesis in apolipoprotein E-deficient (ApoE(-/-)) mice. Mice transgenic for lysozyme (LZ-Tg) are resistant to acute and chronic oxidative stress and have decreased circulating levels of pro-oxidant advanced glycation end-products (AGEs). Herein we report that TIB-186 macrophages transduced with adenovirus-expressing human LZ (AdV-LZ) containing the AGE-binding domain facilitated AGE uptake and degradation and that AdV-LZ-transduced macrophages and peritoneal macrophages from LZ-Tg mice suppressed the AGE-triggered tumor necrosis factor-α response. We assessed atherosclerosis in LZ-Tg mice crossed with ApoE(-/-) mice (LZ/ApoE(-/-)) and found increased serum LZ levels and decreased AGE and 8-isoprostanes levels, although hyperlipidemia remained similar to ApoE(-/-) controls. Atherosclerotic plaques and neointimal lesions at the aortic root and descending aorta were markedly decreased (by 40% and 80%, respectively) in LZ/ApoE (-/-) versus ApoE(-/-) mice, as were inflammatory infiltrates. The arterial lesions following femoral artery injury in LZ/ApoE(-/-) mice were suppressed (intimal to media ratio decreased by 50%), as were AGE deposits and vascular smooth muscle cell activation, compared to ApoE(-/-) mice. Despite hyperlipidemia, development of atheroma and occlusive, inflammatory arterial neointimal lesions in response to injury was suppressed in LZ/ApoE(-/-) mice. This effect may be due to the antioxidant properties of LZ, which is possibly linked to the AGE-binding domain region of the molecule. Copyright © American Society for Investigative Pathology.

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APA

Liu, H., Zheng, F., Li, Z., Uribarri, J., Ren, B., Hutter, R., … Vlassara, H. (2006). Reduced acute vascular injury and atherosclerosis in hyperlipidemic mice transgenic for lysozyme. American Journal of Pathology, 169(1), 303–313. https://doi.org/10.2353/ajpath.2006.050885

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