SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity

Zhihao Liu; Xiaozhi Liu; Li Liu; Ying Wang; Jie Zheng; Lan Li; Sheng Li; Han Zhang; Jingyu Ni; Chuanrui Ma; Xiumei Gao; Xiyun Bian; Guanwei Fan

doi:10.1016/j.jpha.2022.11.010

Volume 13 Issue 2

Mar. 2023

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Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(2): 170-186

Zhihao Liu, Xiaozhi Liu, Li Liu, Ying Wang, Jie Zheng, Lan Li, Sheng Li, Han Zhang, Jingyu Ni, Chuanrui Ma, Xiumei Gao, Xiyun Bian, Guanwei Fan. SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity[J]. Journal of Pharmaceutical Analysis, 2023, 13(2): 170-186. doi: 10.1016/j.jpha.2022.11.010

Citation:

Zhihao Liu, Xiaozhi Liu, Li Liu, Ying Wang, Jie Zheng, Lan Li, Sheng Li, Han Zhang, Jingyu Ni, Chuanrui Ma, Xiumei Gao, Xiyun Bian, Guanwei Fan. SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity[J]. Journal of Pharmaceutical Analysis, 2023, 13(2): 170-186. doi: 10.1016/j.jpha.2022.11.010

Citation:

Zhihao Liu, Xiaozhi Liu, Li Liu, Ying Wang, Jie Zheng, Lan Li, Sheng Li, Han Zhang, Jingyu Ni, Chuanrui Ma, Xiumei Gao, Xiyun Bian, Guanwei Fan. SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity[J]. Journal of Pharmaceutical Analysis, 2023, 13(2): 170-186. doi: 10.1016/j.jpha.2022.11.010

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SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity

doi: 10.1016/j.jpha.2022.11.010

Zhihao Liu^a,b,
Xiaozhi Liu^c,
Li Liu^a,b,
Ying Wang^c,
Jie Zheng^c,
Lan Li^b,d,
Sheng Li^b,
Han Zhang^b,d,
Jingyu Ni^b,d,
Chuanrui Ma^a,
Xiumei Gao^b,d,
Xiyun Bian^{c
,
,},
Guanwei Fan^{a,b,d
,
,}

a. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300193, China;
b. State Key Laboratory of Component-Based Chinese Medicine, Tianjin, 301617, China;
c. Tianjin Key Laboratory of Epigenetics for Organ Development in Preterm Infants, The Fifth Central Hospital of Tianjin, Tianjin, 300450, China;
d. Haihe Laboratory of Modern Chinese Medicine, Tianjin, 301617, China

Funds:

The authors gratefully acknowledge Xiaohui Fan, PhD (Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, China) for assisting with snRNA-seq experiments. The authors thank Wei Yang, PhD (Duke University Medical Center, USA) for providing SUMO1-/- mice. This study was supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (Grant No.: ZYYCXTD-D-202207), the National Natural Science Foundation of China (Grant Nos.: 82270304, 81774050, and 81901526), the Tianjin Special Project of New Generation Artificial Intelligence Technology (Project No.: 18ZXZNSY00260), and the Ministry of Education of People's Republic of China “Program for Innovative Research Team in University” (Project No.: IRT_16R54).

Received Date: Jul. 14, 2022
Accepted Date: Nov. 27, 2022
Rev Recd Date: Nov. 19, 2022
Publish Date: Mar. 07, 2023

Abstract

Abstract

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.
- Myocardial infarction,
- SUMO1,
- SnRNA-seq,
- Cardiomyocyte

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References(60)

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