单细胞与空间组学视角下主动脉夹层血管壁细胞异质性及细胞互作
Cellular Heterogeneity and Intercellular Communication in the Aortic Wall of Aortic Dissection: Insights from Single-Cell and Spatial Omics
摘要: 主动脉夹层(aortic dissection, AD)进展快,血管壁失稳会牵涉到结构细胞状态改变、细胞外基质破坏、免疫炎症反应及异常力学应力等多个环节;单细胞RNA测序和空间组学能把细胞组成、状态变化与组织定位联系起来,补充了传统组织学和批量转录组学在细胞分辨率方面的不足。本综述围绕AD血管壁细胞异质性与细胞互作,梳理血管平滑肌细胞和巨噬细胞等关键细胞的连续表型谱、主要驱动因素及潜在可逆性,归纳趋化、代谢、内皮屏障和细胞外基质重塑相关网络,并把候选生物标志物、实验性干预靶点以及主动脉组织单细胞与空间组学研究的方法学挑战纳入同一框架。现有研究显示,AD血管壁损伤并不是由某一个孤立细胞亚群造成,而是多类结构细胞和免疫细胞在特定空间微环境中持续互作后共同推动病变进展;后续研究还需要在标准化取材、单细胞与单核测序选择、空间组学验证和多组学整合方面继续完善,从而推动细胞图谱发现向机制解释和临床转化延伸。
Abstract: Aortic dissection (AD) is a rapidly progressive aortic disease in which vascular-wall destabilization involves structural-cell remodeling, extracellular matrix disruption, immune inflammation, and abnormal mechanical stress. Single-cell RNA sequencing and spatial omics link cellular composition, state changes, and tissue localization, thereby complementing conventional histology and bulk transcriptomics. This review focuses on cellular heterogeneity and intercellular communication in the dissected aortic wall, summarizes the continuous phenotypic spectra, major driving factors, and potential reversibility of key cell types such as vascular smooth muscle cells and macrophages, integrates interaction networks related to chemotaxis, metabolism, endothelial barrier function, and extracellular matrix remodeling, and incorporates candidate biomarkers, experimental therapeutic targets, and methodological challenges into a unified framework. Current studies suggest that aortic-wall injury in AD is not driven by a single isolated cell subset but by sustained interactions among structural and immune cells within specific spatial microenvironments. Future work should further improve standardized sampling, selection between single-cell and single-nucleus sequencing, spatial validation, and multi-omics integration, so as to advance cellular atlas findings toward mechanistic interpretation and clinical translation.
文章引用:曾照红, 刘峰. 单细胞与空间组学视角下主动脉夹层血管壁细胞异质性及细胞互作[J]. 临床医学进展, 2026, 16(7): 2137-2146. https://doi.org/10.12677/acm.2026.1672742

参考文献

[1] Michel, J.B., Jondeau, G. and Milewicz, D.M. (2018) From Genetics to Response to Injury: Vascular Smooth Muscle Cells in Aneurysms and Dissections of the Ascending Aorta. Cardiovascular Research, 114, 578-589. [Google Scholar] [CrossRef] [PubMed]
[2] Lu, H.S., Sawada, H. and Wu, C. (2022) Aortic Aneurysm and Dissection: Heterogeneity and Molecular Mechanisms. Biomolecules, 12, Article 1536. [Google Scholar] [CrossRef] [PubMed]
[3] Longo, S.K., Guo, M.G., Ji, A.L. and Khavari, P.A. (2021) Integrating Single-Cell and Spatial Transcriptomics to Elucidate Intercellular Tissue Dynamics. Nature Reviews Genetics, 22, 627-644. [Google Scholar] [CrossRef] [PubMed]
[4] Tao, J., Yang, H., Yong, J., Chen, X., Zhao, Q., Wu, X., et al. (2026) Integrated Single‐Cell and Spatial Analysis Reveals a Metabolic‐Immune Axis Driving Aortic Dissection. Advanced Science. [Google Scholar] [CrossRef
[5] Zhang, B., Zeng, K., Guan, R., Jiang, H., Qiang, Y., Zhang, Q., et al. (2023) Single-Cell RNA-Seq Analysis Reveals Macrophages Are Involved in the Pathogenesis of Human Sporadic Acute Type A Aortic Dissection. Biomolecules, 13, Article 399. [Google Scholar] [CrossRef] [PubMed]
[6] Liu, Y., Zou, L., Tang, H., Li, J., Liu, H., Jiang, X., et al. (2022) Single-Cell Sequencing of Immune Cells in Human Aortic Dissection Tissue Provides Insights into Immune Cell Heterogeneity. Frontiers in Cardiovascular Medicine, 9, Article 791875. [Google Scholar] [CrossRef] [PubMed]
[7] Li, Y., Ren, P., Dawson, A., Vasquez, H.G., Ageedi, W., Zhang, C., et al. (2020) Single-Cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns in Control and Aneurysmal Human Aortic Tissue. Circulation, 142, 1374-1388. [Google Scholar] [CrossRef] [PubMed]
[8] Chou, E.L., Chaffin, M., Simonson, B., Pirruccello, J.P., Akkad, A., Nekoui, M., et al. (2022) Aortic Cellular Diversity and Quantitative Genome-Wide Association Study Trait Prioritization through Single-Nuclear RNA Sequencing of the Aneurysmal Human Aorta. Arteriosclerosis, Thrombosis, and Vascular Biology, 42, 1355-1374. [Google Scholar] [CrossRef] [PubMed]
[9] Mizrak, D., Zhao, Y., Feng, H., Macaulay, J., Tang, Y., Sultan, Z., et al. (2023) Single-molecule Spatial Transcriptomics of Human Thoracic Aortic Aneurysms Uncovers Calcification-Related CARTPT-Expressing Smooth Muscle Cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 43, 2285-2297. [Google Scholar] [CrossRef] [PubMed]
[10] Zhang, L., Qiu, Z., Zheng, H., Yang, X., Ye, J., He, J., et al. (2022) Single Cell RNA Sequencing Reveals the Pathogenesis of Aortic Dissection Caused by Hypertension and Marfan Syndrome. Frontiers in Cell and Developmental Biology, 10, Article 880320. [Google Scholar] [CrossRef] [PubMed]
[11] Chen, Y., Zhang, T., Yao, F., Gao, X., Li, D., Fu, S., et al. (2022) Dysregulation of Interaction between LOXhigh Fibroblast and Smooth Muscle Cells Contributes to the Pathogenesis of Aortic Dissection. Theranostics, 12, 910-928. [Google Scholar] [CrossRef] [PubMed]
[12] Wang, Y., Jia, X., Zhang, Y., Zhang, B., Zhou, Y., Li, X., et al. (2025) ACKR1 hiECs Promote Aortic Dissection through Adjusting Macrophage Behavior. Circulation Research, 136, 211-228. [Google Scholar] [CrossRef] [PubMed]
[13] Shao, L., Hu, F., Zhao, L., Luo, J., Zou, P., Liu, X., et al. (2026) Single‐Cell Transcriptomics Reveals Cellular Heterogeneity and Phenotypic Transitions of Smooth Muscle Cells in Aortic Dissection. iMeta, 5, e70124. [Google Scholar] [CrossRef
[14] Rombouts, K.B., van Merrienboer, T.A.R., Ket, J.C.F., Bogunovic, N., van der Velden, J. and Yeung, K.K. (2022) The Role of Vascular Smooth Muscle Cells in the Development of Aortic Aneurysms and Dissections. European Journal of Clinical Investigation, 52, e13697. [Google Scholar] [CrossRef] [PubMed]
[15] Xu, C., Liu, X., Fang, X., Yu, L., Lau, H.C., Li, D., et al. (2022) Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection. Frontiers in Genetics, 13, Article 836593. [Google Scholar] [CrossRef] [PubMed]
[16] Han, Y., Cui, Y., Liu, J., Wang, D., Zou, G., Qi, X., et al. (2024) Single‐Cell RNA‐Seq Reveals Injuries in Aortic Dissection and Identifies PDGF Signalling Pathway as a Potential Therapeutic Target. Journal of Cellular and Molecular Medicine, 28, e70293. [Google Scholar] [CrossRef] [PubMed]
[17] Yao, C., Wang, G., Wu, Q., Pan, Y., Chen, Z., Guo, J., et al. (2025) Gene-Metabolite Interactions in Aortic Dissection: Insights from Metabolic and Single-Cell Analyses. Medicine, 104, e45846. [Google Scholar] [CrossRef
[18] Chen, L., Zhu, Y., Yang, X., Wu, J., Chen, K., Huang, W., et al. (2025) Leptin Aggravates Thoracic Aortic Dissection through Impairment of Energy Metabolism in Nrip2+ Smooth Muscle Cells. Advanced Science, 12, e02027. [Google Scholar] [CrossRef] [PubMed]
[19] Chen, K., Wang, M., Zhang, Z., Chen, Y., Zhu, H., Yang, T., et al. (2026) Loss of CASQ2 Promotes Vascular Smooth Muscle Cell Phenotypic Switching in Aortic Dissection Uncovered by Integrated Single-Cell Transcriptomics. BMC Medical Genomics. [Google Scholar] [CrossRef
[20] Chen, X., Chen, R., Wu, Y., Yu, A., Wang, F., Ying, C., et al. (2024) FABP5+ Macrophages Contribute to Lipid Metabolism Dysregulation in Type A Aortic Dissection. International Immunopharmacology, 143, 113438. [Google Scholar] [CrossRef] [PubMed]
[21] Zhao, S., Hua, X., Zhu, D., Li, P., Cui, H., Sun, Z., et al. (2026) SPP1higH Fibrogenic Macrophages Mediate Protective Fibrotic Remodeling and Promote Vascular Stability in Hypertension-Associated Aortic Dissection. BMC Medicine, 24, Article No. 262. [Google Scholar] [CrossRef
[22] Inoue, T., Emoto, T., Yamanaka, K., Chomei, S., Miyahara, S., Takahashi, H., et al. (2024) Intense Impact of Il-1β Expressing Inflammatory Macrophages in Acute Aortic Dissection. Scientific Reports, 14, Article No. 14893. [Google Scholar] [CrossRef] [PubMed]
[23] Murray, P.J., Allen, J.E., Biswas, S.K., Fisher, E.A., Gilroy, D.W., Goerdt, S., et al. (2014) Macrophage Activation and Polarization: Nomenclature and Experimental Guidelines. Immunity, 41, 14-20. [Google Scholar] [CrossRef] [PubMed]
[24] Yin, Z., Wen, T., Cao, X., Lv, Z., Su, Y., Liang, L., et al. (2025) The Transcription Factor RBPJ Is Required for Inflammatory Macrophage Activation in Thoracic Aortic Dissection by Mediating Mechanotransduction-Induced Glycolysis. Cellular and Molecular Life Sciences, 82, Article No. 370. [Google Scholar] [CrossRef
[25] Zhao, Y., Zuo, Z., Li, Z., Yuan, Y., Hong, S., Fu, W., et al. (2024) Integrated Multi-Omics Profiling Reveals Neutrophil Extracellular Traps Potentiate Aortic Dissection Progression. Nature Communications, 15, Article No. 10736. [Google Scholar] [CrossRef] [PubMed]
[26] Xue, C., Jiang, L., Zhang, B., Sun, J., Zhu, H., Lu, L., et al. (2024) Integrative Analysis Reveals Chemokines CCL2 and CXCL5 Mediated Shear Stress-Induced Aortic Dissection Formation. Heliyon, 10, e23312. [Google Scholar] [CrossRef] [PubMed]
[27] Lin, M., Yan, J., Tang, J., Han, S., Guo, P., Wu, S., et al. (2024) Air Pollutants and Mortality Risk in Patients with Aortic Dissection: Evidence from a Clinical Cohort, Single-Cell Sequencing, and Proteomics. Environmental Science & Technology, 58, 6509-6518. [Google Scholar] [CrossRef] [PubMed]
[28] Pei, Y., Lin, W., Zhang, T., Chu, X., Xu, H., Sun, Y., et al. (2025) Periaortic Lymphatic Vessels Protect against Thoracic Aortic Dissection through Mobilizing Immune Response. Cardiovascular Research, 121, 2594-2609. [Google Scholar] [CrossRef
[29] Cai, X., Li, X., Shi, J., Tang, L., Yang, J., Yu, R., et al. (2025) S100A8/A9 High-Expression Macrophages Mediate Renal Tubular Epithelial Cell Damage in Acute Kidney Injury Following Acute Type A Aortic Dissection Surgery. Frontiers in Molecular Biosciences, 12, Article 1530741. [Google Scholar] [CrossRef] [PubMed]
[30] Armingol, E., Officer, A., Harismendy, O. and Lewis, N.E. (2021) Deciphering Cell-Cell Interactions and Communication from Gene Expression. Nature Reviews Genetics, 22, 71-88. [Google Scholar] [CrossRef] [PubMed]
[31] Dimitrov, D., Türei, D., Garrido-Rodriguez, M., Burmedi, P.L., Nagai, J.S., Boys, C., et al. (2022) Comparison of Methods and Resources for Cell-Cell Communication Inference from Single-Cell RNA-Seq Data. Nature Communications, 13, Article No. 3224. [Google Scholar] [CrossRef] [PubMed]
[32] He, W., Yu, S., Li, J., Li, S., Chen, Z., Zhang, J., et al. (2025) From Inflammation to Remodelling: A Novel BASP1+ Monocyte Subset as a Catalyst for Acute Aortic Dissection. Journal of Advanced Research, 78, 647-666. [Google Scholar] [CrossRef] [PubMed]
[33] He, Y., Jin, H., Zhao, J., Wang, C., Ma, W., Xing, J., et al. (2022) Single-Cell Transcriptomic Analysis Reveals Differential Cell Subpopulations and Distinct Phenotype Transition in Normal and Dissected Ascending Aorta. Molecular Medicine, 28, Article No. 158. [Google Scholar] [CrossRef] [PubMed]
[34] Tang, D., Han, Y., Jiang, H., Uzokov, J., Li, F., Wang, Z., et al. (2026) Single-Cell Transcriptomics Identifies a Pivotal Role of SPHK1+ Macrophage-Driven Inflammation in Mechanism of Aortic Dissection and Highlights SPHK1 as a Therapeutic Target. Inflammation, 49, Article No. 143. [Google Scholar] [CrossRef
[35] Zhu, H., Wu, J., Xu, Z., Pei, Y., Jing, Z., Zhou, J., et al. (2026) Fibroblast Activation Protein Promotes Thoracic Aortic Dissection via PLAUR/ITGB1‐Mediated Pro‐Inflammatory Macrophage Polarization. Advanced Science, 13, e14786. [Google Scholar] [CrossRef
[36] Li, H., Liu, C., Mao, X., Yuan, S., Li, L. and Cong, X. (2024) Identifying HIF1A and HGF as Two Hub Genes in Aortic Dissection and Function Analysis by Integrating RNA Sequencing and Single-Cell RNA Sequencing Data. Frontiers in Cardiovascular Medicine, 11, Article 1475991. [Google Scholar] [CrossRef] [PubMed]
[37] Wang, Y., Gao, P., Li, F. and Du, J. (2022) Insights on Aortic Aneurysm and Dissection: Role of the Extracellular Environment in Vascular Homeostasis. Journal of Molecular and Cellular Cardiology, 171, 90-101. [Google Scholar] [CrossRef] [PubMed]
[38] Liu, Z., Ran, H., Tang, Y., Li, L., Gao, Z., Li, Z., et al. (2026) Revealing FPR1 as a Potential Pathogenic Biomarker for Aortic Dissection Based on Mendelian Randomization, Single-Cell Transcriptome and Clinical Data Analysis. Biology Direct, 21, Article No. 26. [Google Scholar] [CrossRef
[39] Mizrak, D., Feng, H. and Yang, B. (2022) Dissecting the Heterogeneity of Human Thoracic Aortic Aneurysms Using Single-Cell Transcriptomics. Arteriosclerosis, Thrombosis, and Vascular Biology, 42, 919-930. [Google Scholar] [CrossRef] [PubMed]
[40] Cao, G., Qiu, S., Hu, C., Kan, Y., Li, Z., Li, S., et al. (2026) Cross-Species scRNA-Seq Finds Ideal Mouse Models for Aortic Dissection Mechanisms. iScience, 29, 115147. [Google Scholar] [CrossRef