SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity.
SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity.
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SUMO1 基于细胞异质性调节梗塞后心脏修复
DOI：
10.1016/j.jpha.2022.11.010
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发表时间：
2023-03
影响因子：
8.8
通讯作者：
Fan, Guanwei
中科院分区：
文献类型：
--
作者：
Liu, Zhihao;Liu, Xiaozhi;Liu, Li;Wang, Ying;Zheng, Jie;Li, Lan;Li, Sheng;Zhang, Han;Ni, Jingyu;Ma, Chuanrui;Gao, Xiumei;Bian, Xiyun;Fan, Guanwei
小泛素相关修饰剂 (SUMOylation) 是一种动态翻译后修饰，可维持心脏功能，并可防止心脏压力超负荷引起的肥厚反应。然而，心肌梗塞 (MI) 后 SUMO 化的功能以及心脏细胞对 SUMO1 缺陷反应的分子细节尚未确定。在这项研究中，我们证明了 MI 后不同细胞类型和心脏区域中 SUMO1 蛋白的丰度不一致。然而，SUMO1 敲除显着加剧了心肌损伤后的收缩功能障碍和梗塞面积。单核 RNA 测序揭示了 SUMO1 在调节心脏细胞中的不同作用。在心肌细胞中，SUMO1 缺失增加了 MI 后 Nppa+Nppb+Ankrd1+ 心肌细胞亚群的比例。此外，SUMO1 敲除小鼠中成纤维细胞向肌成纤维细胞亚簇的转化受到抑制。重要的是，SUMO1 缺失促进了内皮细胞亚群的增殖，具有重建新血管形成和表达血管生成相关基因的能力。配体/受体相互作用的计算分析提出了介导心肌细胞与内皮细胞通讯的假定途径。预先注射心肌细胞特异性 AAV-SUMO1（而非内皮细胞特异性形式）的小鼠，在 MI 后表现出改善的心脏重塑。总的来说，我们的结果确定了 MI 后 SUMO1 在心肌细胞、成纤维细胞和内皮细胞中的作用。这些发现为 SUMO1 参与 MI 发病机制提供了新的见解，并揭示了新的治疗靶点。 SUMO1 缺乏会加剧心肌损伤后的收缩功能障碍和梗塞面积。 SnRNA-seq 显示梗塞心肌中 SUMO1 信号传导的细胞特异性效应。
Small ubiquitin-related modifier (SUMOylation) is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload. However, the function of SUMOylation after myocardial infarction (MI) and the molecular details of heart cell responses to SUMO1 deficiency have not been determined. In this study, we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI. However, SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury. Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells. Among cardiomyocytes, SUMO1 deletion increased the Nppa+Nppb+Ankrd1+ cardiomyocyte subcluster proportion after MI. In addition, the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice. Importantly, SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes. Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium. Mice preinjected with cardiomyocyte-specific AAV-SUMO1, but not the endothelial cell-specific form, and exhibited ameliorated cardiac remodeling following MI. Collectively, our results identified the role of SUMO1 in cardiomyocytes, fibroblasts, and endothelial cells after MI. These findings provide new insights into SUMO1 involvement in the pathogenesis of MI and reveal novel therapeutic targets. SUMO1 deficiency exacerbated systolic dysfunction and infarct size after myocardial injury. SnRNA-seq showed cell-specific effects of SUMO1 signaling in infarcted myocardium.
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影响因子：
13.6
作者：
Chen, Lihe;Chou, Chun-Lin;Knepper, Mark A.
通讯作者：
Knepper, Mark A.
影响因子：
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作者：
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作者：
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影响因子：
12.4
作者：
Jin, Kaiyu;Gao, Shan;Fan, Xiaohui
通讯作者：
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影响因子：
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作者：
Korsunsky, Ilya;Millard, Nghia;Raychaudhuri, Soumya
通讯作者：
Raychaudhuri, Soumya