[1]张建宁 冼婉泳 张小宇 陶军 夏文豪.基于主动脉组织病理和循环生物标志物评价高血压血管内皮炎症表型变化与内皮功能关系的研究[J].心血管病学进展,2025,(7):652.[doi:10.16806/j.cnki.issn.1004-3934.2025.07.016]
 ZHANG Jianning,XIAN Wanyong,ZHANG Xiaoyu,et al.Evaluation of the Relationship Between Changes in Vascular Endothelial Inflamma tory Phenotype and Endothelial Function in Hypertensi on Based on Aortic Histopathology and Circulating Biomarkers[J].Advances in Cardiovascular Diseases,2025,(7):652.[doi:10.16806/j.cnki.issn.1004-3934.2025.07.016]
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基于主动脉组织病理和循环生物标志物评价高血压血管内皮炎症表型变化与内皮功能关系的研究()

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2025年7期
页码:
652
栏目:
论著
出版日期:
2025-07-25

文章信息/Info

Title:
Evaluation of the Relationship Between Changes in Vascular Endothelial Inflamma tory Phenotype and Endothelial Function in Hypertensi on Based on Aortic Histopathology and Circulating Biomarkers
作者:
张建宁1 冼婉泳2 张小宇1 陶军1 夏文豪1
(中山大学附属第一医院高血压血管病科,广东 广州 510000;2. 佛山市南海区第四人民医院,广东 佛山 528200)
Author(s):
ZHANG Jianning1XIAN Wanyong2ZHANG Xiaoyu1TAO Jun1XIA Wenhao1
Department of Hypertension and Vascular Disease,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510000,Guangdong,China2.The Fourth Peoples Hospital of Foshan Nanhai District,Foshan 528200,Guangdong,China)
关键词:
高血压血管内皮功能炎症标志物巨噬细胞
Keywords:
HypertensionEndothelial functionInflammatory cytokinesMacrophages
DOI:
10.16806/j.cnki.issn.1004-3934.2025.07.016
摘要:
目的 观察巨噬细胞炎症标志物与高血压患者血管内皮功能的关联。 方法 运用高血压患者主动脉组织和高血压小鼠模型,利用免疫荧光技术检测巨噬细胞和炎症因子表达情况,血管环实验评估内皮舒张功能;纳入2020年10月—2022年12月在中山大学附属第一医院诊断为高血压患者96例,记录患者临床特征,采用液相悬浮芯片技术检测血浆中8项炎症因子表达水平,运用血流介导的血管内皮舒张功能(FMD)评估肱动脉内皮功能。根据Spearman相关系数探索炎症标志物与FMD的相关关系。结果 与健康对照组相比,高血压患者主动脉组织CD68+巨噬细胞富集,且肿瘤坏死因子ɑ(TNF-ɑ)、白细胞介素-8(IL-8)表达水平升高(P<0.01)。高血压小鼠的主动脉内皮舒张功能损伤,巨噬细胞数量增多,TNF-ɑ表达上调(P<0.001)。高血压患者外周血中炎症因子间双变量Spearman相关系数结果提示,炎症因子间普遍存在显著相关(P<0.01)。在未校正模型中,FMD与TNF-ɑ(r=-0.252,P=0.013)、IL-8(r=-0.330,P<0.01)呈显著负相关;校正年龄、性别、收缩压、糖尿病、吸烟后,FMD与IL-8(r=-0.301,P=0.018)仍具有显著负性相关关系。结论 高血压患者主动脉 巨噬细胞富集,血浆中IL-8表达水平升高与血管内皮功能障碍相关。
Abstract:
Objective To investigate the associations of macrophage inflammatory markers and endothelial function in hypertensive patients. Methods Using aortic tissue from hypertensive patients and hypertensive mouse models,immunofluorescence technology was used to detect the expression of macrophages and inflammatory factors,and vascular ring experiments were conducted to evaluate endothelial diastolic function. 96 patients diagnosed with hypertension at The First Affiliated Hospital of Sun Yat-sen University from October 2020 to December 2022 were enrolled,and their clinical characteristics were recorded. The expression levels of 8 inflammatory factors in plasma were detected using liquid-phase suspension chip technology, and the endothelial function of the brachial artery was evaluated using flow-mediated vasodilation(FMD). Exploring the correlation between inflammatory markers and FMD based on Spearman correlation coefficient. Results Compared with the healthy control group,hypertensive patients showed an enrichment of CD68+ macrophages in aortic tissue,and an increase in the expression levels of tumor necrosis factor ɑ (TNF -ɑ) and interleukin-8(IL-8) (P<0.01). The aortic endothelial relaxation function of hypertensive mice is impaired,the number of macrophages increases,and the expression of TNF-ɑ is upregulated( P<0.001). The bivariate Spearman correlation coefficient between inflammatory factors in peripheral blood of hypertensive patients suggests that there is a significant correlation between inflammatory factors(P<0.01). In the uncorrected model,FMD was significantly negatively correlated with TNF -α(r=-0.252,P=0.013) and IL-8 (r=-0.330,P<0.01). After adjusting for age,sex,systolic blood pressure,diabetes and smoking,FMD still had a significant negative correlation with IL-8 (r=-0.301,P=0.018). Conclusion Elevated levels of IL-8 expression in plasma and enriched macrophages in the aorta of hypertensive patients are associated with endothelial dysfunction

参考文献/References:

[1] Mills KT,Bundy JD,Kelly TN,et al. Global disparities of hypertension prevalence and control:a systematic analysis of population-based studies from 90 countries[J]. Circulation,2016,134(6):441-450.

[2] NCD Risk Factor Collaboration(NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019:a pooled analysis of 1201 population-representative studies with 104 million participants[J]. Lancet,2021,398(10304):957-980.

[3] 国家心血管病中心. 中国心血管健康与疾病报告2023[M]. 北京:中国协和医科大学出版社,2024.

[4] Eelen G,de Zeeuw P,Simons M,et al. Endothelial cell metabolism in normal and diseased vasculature[J]. Circ Res,2015,116(7):1231-1244.

[5] Gimbrone MA,García-Carde?a G. Endothelial cell dysfunction and the pathobiology of atherosclerosis[J]. Circ Res,2016,118(4):620-636.

[6] Thijssen DHJ,Bruno RM,van Mil ACCM,et al. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans[J]. Eur Heart J,2019,40(30):2534-2547.

[7] Alexander Y,Osto E,Schmidt-Trucks?ss A,et al. Endothelial function in cardiovascular medicine:a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology,Aorta and Peripheral Vascular Diseases,Coronary Pathophysiology and Microcirculation,and Thrombosis[J]. Cardiovasc Res,2021,117(1):29-42.

[8] Xiao L,Harrison DG. Inflammation in hypertension[J]. Can J Cardiol,2020,36(5):635-647.

[9] Zhang Z,Zhao L,Zhou X,et al. Role of inflammation,immunity,and oxidative stress in hypertension:new insights and potential therapeutic targets[J]. Front Immunol,2022,13:1098725.

[10] Guzik TJ,Nosalski R,Maffia P,et al. Immune and inflammatory mechanisms in hypertension[J]. Nat Rev Cardiol,2024,21(6):396-416.

[11] Zhao G,Lu H,Chang Z,et al. Single-cell RNA sequencing reveals the cellular heterogeneity of aneurysmal infrarenal abdominal aorta[J]. Cardiovasc Res,2021,117(5):1402-1416.

[12] Vita JA,Keaney JF,Larson MG,et al. Brachial artery vasodilator function and systemic inflammation in the Framingham Offspring Study[J]. Circulation,2004,110(23):3604-3609.

[13] Weiner SD,Ahmed HN,Jin Z,et al. Systemic inflammation and brachial artery endothelial function in the Multi-Ethnic Study of Atherosclerosis(MESA)[J]. Heart,2014,100(11):862-866.

[14] Junqueira CLC,Magalh?es MEC,Brand?o AA,et al. Evaluation of endothelial function by VOP and inflammatory biomarkers in patients with arterial hypertension[J]. J Hum Hypertens,2018,32(2):105-113.

[15] Jian ZW,Zhang XM,Huang GS. Clinical value of the platelet and inflammatory factor activation in vascular endothelial injury in essential hypertension[J]. Clin Hemorheol Microcirc,2023,83(2):171-180.

[16] 《中国高血压防治指南》修订委员会. 中国高血压防治指南(2018年修订版)[M]. 北京:中国医药科技出版社,2018.

[17] Corretti MC,Anderson TJ,Benjamin EJ,et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery:a report of the International Brachial Artery Reactivity Task Force[J]. J Am Coll Cardiol,2002,39(2):257-265.

[18] Chen L,Ding ML,Wu F,et al. Impaired endothelial repair capacity of early endothelial progenitor cells in hypertensive patients with primary hyperaldosteronemia:role of 5,6,7,8-tetrahydrobiopterin oxidation and endothelial nitric oxide synthase uncoupling[J]. Hypertension,2016,67(2):430-439.

[19] Gutiérrez E,Flammer AJ,Lerman LO,et al. Endothelial dysfunction over the course of coronary artery disease[J]. Eur Heart J,2013,34(41):3175-3181.

[20] Xu S,Ilyas I,Little PJ,et al. Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond:from mechanism to pharmacotherapies[J]. Pharmacol Rev,2021,73(3):924-967.

[21] Ma J,Li Y,Yang X,et al. Signaling pathways in vascular function and hypertension:molecular mechanisms and therapeutic interventions[J]. Signal Transduct Target Ther,2023,8(1):168.

[22] Totoń-?urańska J,Mikolajczyk TP,Saju B,et al. Vascular remodelling in cardiovascular diseases:hypertension,oxidation,and inflammation[J]. Clin Sci(Lond),2024,138(13):817-850.

[23] Zhao J,Andreev I,Silva HM. Resident tissue macrophages:key coordinators of tissue homeostasis beyond immunity[J]. Sci Immunol,2024,9(94):eadd1967.

[24] Yunna C,Mengru H,Lei W,et al. Macrophage M1/M2 polarization[J]. Eur J Pharmacol,2020,877:173090.

[25] Hou P,Fang J,Liu Z,et al. Macrophage polarization and metabolism in atherosclerosis[J]. Cell Death Dis,2023,14(10):691.

[26] Bloom SI,Islam MT,Lesniewski LA,et al. Mechanisms and consequences of endothelial cell senescence[J]. Nat Rev Cardiol,2023,20(1):38-51.

[27] Li X,Chen X,Zheng L,et al. Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response[J]. Acta Pharm Sin B,2023,13(12):4765-4784.

[28] Zhang J,Muri J,Fitzgerald G,et al. Endothelial lactate controls muscle regeneration from ischemia by inducing M2-like macrophage polarization[J]. Cell Metab,2020,31(6):1136-1153.

[29] Nawawi H,Osman NS,Annuar R,et al. Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin[J]. Atherosclerosis,2003,169(2):283-291.

[30] Kovacs I,Toth J,Tarjan J,et al. Correlation of flow mediated dilation with inflammatory markers in patients with impaired cardiac function. Beneficial effects of inhibition of ACE[J]. Eur J Heart Fail,2006,8(5):451-459.

[31] Emamat H,Asadian S,Zahedmehr A,et al. The effect of barberry(Berberis vulgaris) consumption on flow-mediated dilation and inflammatory biomarkers in patients with hypertension:a randomized controlled trial [J]. Phytother Res,2021,35(5):2607-2615.

[32] Ridker PM,Everett BM,Thuren T,et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease[J]. N Engl J Med,2017,377(12):1119-1131.

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更新日期/Last Update: 2025-09-30