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Lipid Droplet Protein PLIN1 Regulates Inflammatory Polarity in Human Macrophages and is Involved in Atherosclerotic Plaque Development by Promoting Stable Lipid Storage

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Title: Lipid Droplet Protein PLIN1 Regulates Inflammatory Polarity in Human Macrophages and is Involved in Atherosclerotic Plaque Development by Promoting Stable Lipid Storage
Authors: Cho, Kyu Yong Browse this author
Miyoshi, Hideaki Browse this author
Nakamura, Akinobu Browse this author
Greenberg, Andrew S. Browse this author
Atsumi, Tatsuya Browse this author →KAKEN DB
Keywords: Atherosclerosis
Macrophages
Inflammation
Lipid droplet protein
Perilipin
Issue Date: 1-Feb-2023
Publisher: Japan Atherosclerosis Society
日本動脈硬化学会
Journal Title: Journal of atherosclerosis and thrombosis
Volume: 30
Issue: 2
Start Page: 170
End Page: 181
Publisher DOI: 10.5551/jat.63153
Abstract: Aim: Perilipins (PLINs), peripheral lipid droplet (LD) proteins, play important roles in lipid accumulation and maturation in adipocytes. The relationship between PLIN family proteins and macrophage polarization in atherosclerosis has not been elucidated. Methods: The experiments used tissues from human arteries of 65 patients who had undergone a carotid endarterectomy, and cultured macrophages generated from healthy human peripheral blood mononuclear cells. Results: Plaque immunohistochemistry demonstrated co-expression of PLIN1 and PLIN2 in both symptomatic (n=31) and asymptomatic patients (n=34). PLIN2 mRNA expression increased 3.38-fold in the symptomatic group compared with those from asymptomatic. PLIN1 was not expressed on small LDs at a shorter incubation but was on large LDs at longer incubation with oxidized LDL and VLDL, while PLIN2 was observed after 24 h and increased with a longer incubation in cultured M1 macrophage. In M2 macrophages, PLIN1 was seen as early as 24 h following incubation with VLDL, and LD size increased with longer incubation. PLIN1 overexpression increased the size of LDs in M1 macrophages, even after a short incubation, and reduced the RNA expression of TNFA, MMP2, ABCA1, and ABCG1 versus the M1 control. Conversely, silencing of PLIN1 in M2 macrophages had the opposite effects on LD size and RNA expression. Conclusion: There was a relationship between macrophage polarity, cytosolic LD size, and PLIN1/PLIN2 expression levels. PLIN2 was mainly expressed in arterial plaques in symptomatic stroke patients, and associated with the inflammatory phenotype of human macrophages, while PLIN1 expression is closely associated with plaque stability and the anti-inflammatory phenotype.
Type: article
URI: http://hdl.handle.net/2115/88933
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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