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RETRACTED ARTICLE: Estradiol Inhibits Cytokine-Induced Expression of VCAM-1 and ICAM-1 in Cultured Human Endothelial Cells Via AMPK/PPARα Activation

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This article was retracted on 19 October 2022

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Abstract

Expression of cell adhesion molecules by vascular endothelial cells (ECs) plays an important role in migration and adhesion of leukocytes into the surrounding tissues, which is a vital step in inflammation and atherogenesis. Estradiol (E2), a human sex hormone and steroid, has differential anti-inflammatory properties, increases arterial vasodilation, inhibits the cellular response to vascular injury, and prevents atherosclerosis. However, the related mechanisms are poorly understood. Here, we studied the effect of E2 on expression of endothelial leukocyte adhesion molecules by cytokine-stimulated human aortic endothelial cells (HAECs). Pre-treatment of HAEC with E2 inhibited tumor necrosis factor-α (TNFα)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) in a time- and dose-dependent manner. E2 at 10 nmol/L inhibited interleukin-1 (IL-1)-stimulated expression of VCAM-1 and ICAM-1. The effect of E2 on cytokine-stimulated VCAM-1 expression was more prominent than that of ICAM-1. E2 reduced TNF-induced mRNA expression of VCAM-1 and ICAM-1. Repressed expression of VCAM-1 and ICAM-1 was associated with decreased adherence of lymphocytes and monocytes to cytokine-stimulated HAEC. E2 suppressed TNF-induced activation of nuclear factor-κB (NF-κB) in HAEC. Importantly, E2 improved AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα) expression in HAEC. Pharmaceutical inhibition of AMPK and PPARα blocks the effect of E2 on NF-κB, VCAM-1, and ICAM-1. These results indicate that E2 may have anti-inflammatory properties in ECs. The anti-inflammatory and anti-atherogenic properties of E2 may partly be ascribed to an effect on activation of AMPK and PPARα and subsequent inhibition of TNF-induced NF-κB activation, leading to the decreased expression of VCAM-1 and ICAM-1. Our findings support further investigations on the therapeutic benefits of E2 in several pathological events involving endothelial dysfunction and atherosclerosis.

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Authors and Affiliations

  1. Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, 130033, Jilin Province, People’s Republic of China

    Xuhui Hou

  2. Department of Cardiology, First Hospital of Jilin University, No.71 Xinmin Street, Changchun, 130021, Jilin Province, People’s Republic of China

    Fei Pei

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  1. Xuhui Hou
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  2. Fei Pei
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Correspondence to Fei Pei.

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Hou, X., Pei, F. RETRACTED ARTICLE: Estradiol Inhibits Cytokine-Induced Expression of VCAM-1 and ICAM-1 in Cultured Human Endothelial Cells Via AMPK/PPARα Activation. Cell Biochem Biophys 72, 709–717 (2015). https://doi.org/10.1007/s12013-015-0522-y

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  • DOI: https://doi.org/10.1007/s12013-015-0522-y

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