质谱学报2025，Vol.46Issue(6)：838-848,11.DOI:10.7538/zpxb.2025.0090
基于有机质谱流式的高血压大鼠心脏单细胞代谢组学研究
Single-Cell Metabolomic of Hypertensive Rats Heart Based on Organic Mass Cytometry
摘要
Abstract
Hypertension is a common chronic cardiovascular disease and one of the major risk factors for cardiovascular mortality and disability,with a global prevalence of approximately 15%.This high incidence not only leads to a substantial disease burden but also gives rise to long-term complications that affect the quality of life of millions worldwide.Surveys indicate that the prevalence of hypertension in China is 27.5%and exhibits an annual upward trend,a situation that poses significant challenges to socioeconomic development including increased healthcare costs and reduced workforce productivity,and imposes immense pressure on public health systems.Due to the high heterogeneity among different individual cells,where even cells of the same type can exhibit distinct functional and molecular profiles,and the involvement of multiple cell types in the synergistic regulation of hypertension pathogenesis,it is crucial to explore the regulatory mechanisms of hypertension at the single-cell level.Single-cell metabolomics,a cutting-edge analytical approach,reveals the metabolic characteristics of individual cells by systematically analyzing endogenous small molecules(metabolites)within cells.By capturing the unique metabolic fingerprints of each cell,single-cell metabolomics can directly reflect metabolic disturbances under pathological conditions,offering valuable insights into the early and subtle changes that precede overt disease manifestations.Hypertension-induced myocardial metabolic dysregulation represents a critical pathological basis for cardiovascular diseases,yet its single-cell metabolic signatures remain incompletely characterized.This study established a novel single-cell metabolomics approach for hypertensive hearts using organic mass cytometry(CyESI-MS),aiming to clarify the metabolic regulatory mechanism from a single-cell perspective.Through optimized tissue dissociation protocols,high-viability single-cell suspensions were prepared from spontaneously hypertensive rats(SHR)and normotensive controls,followed by metabolomics analysis via CyESI-MS.As a result,70 endogenous metabolites are identified at the single-cell level,with 34 demonstrating significant alterations(|log2FC|≥1,p<0.05).Pathway enrichment analysis reveals five core dysregulated metabolic pathways,including glycerophospholipid metabolism,biosynthesis of phenylalanine,tyrosine and tryptophan,phenylalanine metabolism,histidine metabolism,and taurine and hypotaurine metabolism.This study employed a single-cell metabolomics approach based on mass spectrometry to delve into metabolic changes in rat heart cells under hypertensive conditions,a phenomenon that is often overlooked in large-scale metabolomics studies based on bulk cells or tissue/organ samples.Furthermore,from the perspective of single-cell metabolomics,this research uncovers the metabolic characteristics of individual heart cells under hypertension,thereby providing important reference value for the early diagnosis of hypertension cardiovascular diseases.This study provides the first single-cell evidence of characteristic metabolic reprogramming in hypertensive hearts,offering new insights into cardiovascular disease mechanisms.关键词
有机质谱流式(CyESI-MS)/高血压/心脏细胞/单细胞代谢组学/生物标志物Key words
organic mass cytometry(CyESI-MS)/hypertension/heart cells/single-cell metabolomics/biomarkers分类
化学引用本文复制引用
曾海深,谢宇君,林俊浩,徐蕙,刘宁,杨运云,靳利利,邓洁薇,栾天罡..基于有机质谱流式的高血压大鼠心脏单细胞代谢组学研究[J].质谱学报,2025,46(6):838-848,11.基金项目
国家自然科学基金(22127810) （22127810）
广东省基础与应用基础研究基金(2024A1515010883,2023A1515012261) （2024A1515010883,2023A1515012261）
广州市基础与应用基础研究专题(2024A04J6429) （2024A04J6429）
广州中医药大学院校联合科技创新基金项目(GZYSE2024G04) （GZYSE2024G04）
广东省第二中医院科研创新基金项目(SEZYY2023B18) （SEZYY2023B18）
广东工业大学智慧医疗创新技术中心专项(ZYZX24-012) （ZYZX24-012）
