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• W2340759610 abstract "Objective— During inflammation, P-selectin expressed on activated endothelial cells and platelets mediates rolling adhesion of leukocytes. Atherosclerosis-prone mice crossed with P-selectin–deficient ( Selp −/− ) mice develop smaller lesions. Cytokines, such as tumor necrosis factor-α, increase Selp transcripts and augment atherosclerosis in mice. However, they decrease SELP transcripts in humans, challenging assumptions that human P-selectin is atherogenic. We used mice expressing a human SELP transgene to examine the atherogenic role of P-selectin. Approach and Results— We crossed apolipoprotein E–deficient ( Apoe −/− ) mice with Selp −/− mice or transgenic mice expressing the entire human SELP gene ( TgSELP +/− ). Aortas developed larger, macrophage-rich atheromas in Apoe −/− Selp −/− TgSELP +/− mice than in Apoe −/− Selp −/− mice after 8 or 16 weeks on a Western diet. Confocal microscopy of Apoe −/− Selp −/− TgSELP +/− aortas revealed staining for human P-selectin in endothelial cells overlying atheromas but not in lesional macrophages. We also observed staining for human P-selectin in aortic endothelial cells of 3- to 4-week-old Apoe −/− Selp −/− TgSELP +/− weanlings before atheromas developed. Furthermore, human SELP transcripts were ≈3-fold higher in aortas of Apoe −/− Selp +/− TgSELP +/− weanlings than in Selp +/− TgSELP +/− weanlings, whereas murine Selp and Sele transcripts were equivalent in weanlings of both genotypes. Human SELP transcripts in aortas of Apoe −/− Selp +/− TgSELP +/− mice remained nearly constant during 16 weeks on a Western diet, whereas murine Selp and Sele transcripts progressively increased. Bone marrow transplantation in Apoe −/− Selp −/− and Apoe −/− Selp −/− TgSELP +/− mice demonstrated that both platelets and endothelial cells must express human P-selectin to promote atherogenesis. Conclusions— P-selectin expressed by human SELP is atherogenic in Apoe −/− mice, suggesting that P-selectin contributes to atherogenesis in humans." @default.
• W2340759610 created "2016-06-24" @default.
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• W2340759610 date "2016-06-01" @default.
• W2340759610 modified "2023-09-27" @default.
• W2340759610 title "P-Selectin Expressed by a Human <i>SELP</i> Transgene Is Atherogenic in Apolipoprotein E–Deficient Mice" @default.
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• W2340759610 doi "https://doi.org/10.1161/atvbaha.116.307437" @default.
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