Genetic ablation of myeloid integrin α9 attenuates early atherosclerosis.

IF 3.6 3区医学 Q3 CELL BIOLOGY

Journal of Leukocyte Biology Pub Date : 2024-11-04 DOI:10.1093/jleuko/qiae161

Tarun Barbhuyan, Rakesh B Patel, Ivan Budnik, Anil K Chauhan

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引用次数: 0

Abstract

Integrin α9β1 is known to stabilize leukocyte adhesion to the activated endothelium. We determined the role of myeloid cell α9β1 in early atherosclerosis in two models: α9Mye-KOApoe-/- or the Ldlr-/- mice transplanted with bone marrow (BM) from α9Mye-KO mice fed a high-fat "Western" diet for 4 wk. α9Mye-KOApoe-/- mice exhibited reduced early lesions in the aortae and aortic sinuses (P < 0.05 vs α9WT Apoe-/- mice). Similar results were obtained in α9Mye-KO BM→Ldlr-/- mice (P < 0.05 vs α9WT BM→Ldlr-/- mice). Reduced early atherosclerosis in α9Mye-KOApoe-/- mice was associated with decreased neutrophil and neutrophil extracellular traps (NETs) content in the aortic lesions (P < 0.05 vs α9WTApoe-/-). Vascular cell adhesion molecule-1-stimulated neutrophils from α9Mye-KO mice exhibited reduced adhesion, transmigration, and NETs formation (NETosis) (P < 0.05 vs α9WT neutrophils). Reduced NETosis was associated with decreased extracellular signal-regulated kinase phosphorylation, peptidyl arginine deiminase 4, and citrullinated histone H3 expression. In summary, genetic ablation of myeloid cell-specific α9 reduces early atherosclerosis, most likely by reducing neutrophil adhesion, transmigration, and NETosis.

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髓系整合素α9的基因消减可减轻早期动脉粥样硬化。

众所周知，整合素α9β1能稳定白细胞对活化内皮的粘附。我们在两种模型中确定了髓细胞α9β1在早期动脉粥样硬化中的作用：α9MyeKOApoe-/-小鼠或移植了α9Mye-KO小鼠骨髓（BM）的Ldlr-/-小鼠，喂食高脂 "西式 "饮食四周。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Leukocyte Biology 医学-免疫学

CiteScore

11.50

自引率

0.00%

发文量

358

审稿时长

2 months

期刊介绍： JLB is a peer-reviewed, academic journal published by the Society for Leukocyte Biology for its members and the community of immunobiologists. The journal publishes papers devoted to the exploration of the cellular and molecular biology of granulocytes, mononuclear phagocytes, lymphocytes, NK cells, and other cells involved in host physiology and defense/resistance against disease. Since all cells in the body can directly or indirectly contribute to the maintenance of the integrity of the organism and restoration of homeostasis through repair, JLB also considers articles involving epithelial, endothelial, fibroblastic, neural, and other somatic cell types participating in host defense. Studies covering pathophysiology, cell development, differentiation and trafficking; fundamental, translational and clinical immunology, inflammation, extracellular mediators and effector molecules; receptors, signal transduction and genes are considered relevant. Research articles and reviews that provide a novel understanding in any of these fields are given priority as well as technical advances related to leukocyte research methods.