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左心房单细胞转录组学揭示双调蛋白可作为心房颤动的替代标志物。

Left atrial single-cell transcriptomics reveals amphiregulin as a surrogate marker for atrial fibrillation.

作者信息

Suzuki Yuya, Emoto Takuo, Sato Shunsuke, Yoshida Takeshi, Shoda Mitsuhiko, Endoh Hiromi, Nagao Manabu, Hamana Tomoyo, Inoue Taishi, Hayashi Tomohiro, Nitta Eriko, Konishi Hiroki, Kiuchi Kunihiko, Takami Mitsuru, Imamura Kimitake, Taniguchi Masayuki, Inoue Masatoshi, Nakamura Toshihiro, Sonoda Yusuke, Takahara Hiroyuki, Nakasone Kazutaka, Yamamoto Kyoko, Tani Kenichi, Iwai Hidehiro, Nakanishi Yusuke, Yonehara Shogo, Murakami Atsushi, Toh Ryuji, Ohkawa Takenao, Furuyashiki Tomoyuki, Nitta Ryo, Yamashita Tomoya, Hirata Ken-Ichi, Fukuzawa Koji

机构信息

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Division of Cardiovascular Surgery, Department of Surgery, Yodogawa Christian Hospital, Osaka, Japan.

出版信息

Commun Biol. 2024 Dec 2;7(1):1601. doi: 10.1038/s42003-024-07308-w.

Abstract

Atrial fibrillation (AF) is strongly associated with strokes, heart failure, and increased mortality. This study aims to identify the monocyte-macrophage heterogeneity and interactions of these cells with non-immune cells, and to identify functional biomarkers in patients with AF. Therefore, we assess the single cell landscape of left atria (LA), using a combination of single cell and nucleus RNA-seq. Myeloid cells in LA tissue are categorized into five macrophage clusters, three monocyte clusters, and others. Cell-Chat analysis revealed that monocytes and IL1B macrophages send epidermal growth factor (EGF) signals to fibroblasts. Amphiregulin (AREG) is the most upregulated gene in monocytes and IL1B macrophages in the AF group, compared with healthy controls from other groups. Serum AREG levels are higher in patients with persistent AF. These data suggested that EGF signaling pathway could be a therapeutic target for AF and serum AREG levels provide an effective biomarker for predicting persistent AF.

摘要

心房颤动(AF)与中风、心力衰竭及死亡率增加密切相关。本研究旨在识别单核细胞-巨噬细胞的异质性以及这些细胞与非免疫细胞的相互作用,并确定房颤患者的功能性生物标志物。因此,我们结合单细胞和细胞核RNA测序评估左心房(LA)的单细胞图谱。LA组织中的髓样细胞分为五个巨噬细胞簇、三个单核细胞簇及其他细胞簇。细胞间通讯分析显示,单核细胞和IL1B巨噬细胞向成纤维细胞发送表皮生长因子(EGF)信号。与其他组的健康对照相比,AF组单核细胞和IL1B巨噬细胞中上调最明显的基因是双调蛋白(AREG)。持续性AF患者的血清AREG水平更高。这些数据表明,EGF信号通路可能是AF的治疗靶点,血清AREG水平为预测持续性AF提供了一种有效的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71f3/11612213/b329f630df50/42003_2024_7308_Fig1_HTML.jpg

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