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已发表论文
SULF1 在内皮细胞衰老和动脉粥样硬化中的作用：来自单细胞和整体转录组学的见解
Authors Jiang MT , Wan SL, Shen XY, Zhang ZB, He ZQ, Hu YX, Liang C
Received 18 June 2025
Accepted for publication 6 December 2025
Published 16 December 2025 Volume 2025:18 Pages 17677—17692
DOI https://doi.org/10.2147/JIR.S544852
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Durga Misra
Meng-Ting Jiang,1,* Shi-Lei Wan,1,* Xiang-Yu Shen,1,* Zhong-Bai Zhang,1 Zhi-Qing He,1 Yang-Xi Hu,1– 4 Chun Liang1
1Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai Cardiovascular Institute of Integrative Medicine, Shanghai, 200003, People’s Republic of China; 2Department of Cardiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 3Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing, 400042, People’s Republic of China; 4Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, 400042, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Chun Liang, Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai Cardiovascular Institute of Integrative Medicine, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86-21-81885291, Email chunliangliang1985@163.com Yang-Xi Hu, Department of Cardiology, Daping Hospital, Army Medical University, 10 Changjiang Branch Road, Chongqing, 400042, People’s Republic of China, Tel +86-21-81512526, Email yxhu@smmu.edu.cn
Background: Endothelial cells (ECs) senescence has emerged as a critical factor in the pathogenesis of atherosclerosis, contributing to vascular aging and plaque formation. However, the molecular mechanisms underlying endothelial senescence in atherosclerosis remain poorly understood.
Methods: Single-cell RNA sequencing (scRNA-seq) data from atherosclerotic core plaques and adjacent normal tissues were analyzed using the Seurat package to identify cell subpopulations and senescence markers. RNA-seq data from early and late atherosclerotic plaques were used for differential gene expression analysis. Subsequently, the candidate gene was identified and validated in the atherosclerotic plaques of ApoE−/− mice and ox-LDL-treated human aortic ECs (HAECs) through siRNA knockdown, Western blot, RT-qPCR, and β-galactosidase staining in vitro.
Results: Single-cell analysis revealed elevated levels of senescence markers in ECs within atherosclerotic plaques. Combined with bulk RNA-seq analysis, SULF1 was identified as a key gene associated with EC senescence. Increased Sulf1 expression was uncovered in the ECs of atherosclerotic plaques in high-fat-fed ApoE−/− mice. In vitro, SULF1 expression was found significantly upregulated in senescent HAECs. Knockdown of SULF1 reversed ox-LDL-induced senescence in HAECs, as shown by reduced expression of senescence markers and improved cell migration in wound healing assays.
Conclusion: This study highlights the critical role of endothelial senescence in atherosclerosis and identifies SULF1 as a key contributor to endothelial senescence and atherogenesis. Targeting SULF1 may be a potential therapeutic strategy for mitigating EC senescence and atherosclerosis.
Keywords: atherosclerosis, endothelial senescence, single-cell RNA sequencing, RNA sequencing, SULF1
1Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai Cardiovascular Institute of Integrative Medicine, Shanghai, 200003, People’s Republic of China; 2Department of Cardiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 3Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease Research, Ministry of Education of China, Chongqing, 400042, People’s Republic of China; 4Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology, Chongqing, 400042, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Chun Liang, Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai Cardiovascular Institute of Integrative Medicine, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86-21-81885291, Email chunliangliang1985@163.com Yang-Xi Hu, Department of Cardiology, Daping Hospital, Army Medical University, 10 Changjiang Branch Road, Chongqing, 400042, People’s Republic of China, Tel +86-21-81512526, Email yxhu@smmu.edu.cn
Background: Endothelial cells (ECs) senescence has emerged as a critical factor in the pathogenesis of atherosclerosis, contributing to vascular aging and plaque formation. However, the molecular mechanisms underlying endothelial senescence in atherosclerosis remain poorly understood.
Methods: Single-cell RNA sequencing (scRNA-seq) data from atherosclerotic core plaques and adjacent normal tissues were analyzed using the Seurat package to identify cell subpopulations and senescence markers. RNA-seq data from early and late atherosclerotic plaques were used for differential gene expression analysis. Subsequently, the candidate gene was identified and validated in the atherosclerotic plaques of ApoE−/− mice and ox-LDL-treated human aortic ECs (HAECs) through siRNA knockdown, Western blot, RT-qPCR, and β-galactosidase staining in vitro.
Results: Single-cell analysis revealed elevated levels of senescence markers in ECs within atherosclerotic plaques. Combined with bulk RNA-seq analysis, SULF1 was identified as a key gene associated with EC senescence. Increased Sulf1 expression was uncovered in the ECs of atherosclerotic plaques in high-fat-fed ApoE−/− mice. In vitro, SULF1 expression was found significantly upregulated in senescent HAECs. Knockdown of SULF1 reversed ox-LDL-induced senescence in HAECs, as shown by reduced expression of senescence markers and improved cell migration in wound healing assays.
Conclusion: This study highlights the critical role of endothelial senescence in atherosclerosis and identifies SULF1 as a key contributor to endothelial senescence and atherogenesis. Targeting SULF1 may be a potential therapeutic strategy for mitigating EC senescence and atherosclerosis.
Keywords: atherosclerosis, endothelial senescence, single-cell RNA sequencing, RNA sequencing, SULF1