High-Dimensional Single-Cell Mass Cytometry Demonstrates Differential Platelet Functional Phenotypes in Infants With Congenital Heart Disease.

IF 7.4 1区 医学 Q1 HEMATOLOGY Arteriosclerosis, Thrombosis, and Vascular Biology Pub Date : 2024-08-22 DOI:10.1161/ATVBAHA.124.321131
Sean X Gu, Brian S Marcus, Vivian W Gu, Adarsh P Varghese, John Hwa, E Vincent S Faustino
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Abstract

Background: Congenital heart disease (CHD) is a group of complex heart defects associated with hematologic abnormalities, including increased risk of thrombotic and bleeding events. Past studies have observed evidence of platelet hyperreactivity, while other studies showed decreased platelet activation in patients with CHD. The goal of this study was to develop a mass spectrometry approach to characterize single platelets in infants with CHD and identify potential etiology for such discrepant results.

Methods: We enrolled 19 infants with CHD along with 21 non-CHD controls at Yale New Haven Children's Heart Center. A single-cell high-dimensional mass cytometry method was developed to quantitatively interrogate platelet surface markers in whole blood. Additionally, plasma cytokine analysis was performed through a multiplexed panel of 52 vascular and inflammatory markers to assess for platelet releasates.

Results: We found that infants with CHD had significant differences in platelet activation and functional markers by mass cytometry compared with non-CHD controls. Based on cell surface markers, we classified the platelets into 8 subpopulations (P0 to P7). Distinct subpopulations of platelets (P1, P4, and P5) exhibiting decreased aggregatory phenotype but altered secretory phenotypes were also identified and found to be more abundant in the blood of infants with CHD. Electron microscopy identified increased proportion of hypogranular platelets in CHD. Moreover, cytokine analysis demonstrated an overall increase in plasma cytokines and biomarkers in CHD, including IL (interleukin)-6, IL-8, IL-27, RANTES, and VWF (von Willebrand factor), which are expressed in platelet granules and can be released upon activation.

Conclusions: We developed a robust mass cytometry approach to identify platelet phenotypic heterogeneity. Infants with CHD had alterations in distinct subpopulations of platelets with overall reduced aggregatory phenotype and secretory dysfunction. These findings suggest that platelets in infants with CHD may be exhausted due to persistent stimulation and may explain both bleeding and thrombotic vascular complications associated with CHD.

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高维单细胞质量细胞测量法显示先天性心脏病婴儿的血小板功能表型存在差异
背景:先天性心脏病(CHD)是一组复杂的心脏缺陷,与血液学异常有关,包括血栓和出血事件风险增加。过去的研究观察到血小板高反应性的证据,而其他研究则显示 CHD 患者的血小板活化程度降低。本研究的目的是开发一种质谱方法来表征患有先天性心脏病的婴儿的单个血小板,并找出造成这种差异结果的潜在病因:我们在耶鲁纽黑文儿童心脏中心招募了 19 名患有先天性心脏病的婴儿和 21 名非先天性心脏病对照组婴儿。我们开发了一种单细胞高维质谱法来定量检测全血中的血小板表面标记物。此外,还通过一个包含 52 种血管和炎症标记物的多重面板进行了血浆细胞因子分析,以评估血小板释放物:结果:我们发现,与非先天性心脏病对照组相比,患有先天性心脏病的婴儿通过质谱细胞计数法检测的血小板活化和功能标记物存在显著差异。根据细胞表面标记物,我们将血小板分为 8 个亚群(P0 至 P7)。我们还发现,患有先天性心脏病的婴儿血液中血小板亚群(P1、P4 和 P5)的聚集表型有所降低,但分泌表型有所改变,而且数量更多。电子显微镜检查发现 CHD 患儿血小板颗粒减少的比例增加。此外,细胞因子分析表明,CHD患者血浆细胞因子和生物标志物总体增加,包括IL(白细胞介素)-6、IL-8、IL-27、RANTES和VWF(von Willebrand因子),它们在血小板颗粒中表达,可在激活时释放:结论:我们开发了一种稳健的质谱方法来识别血小板表型异质性。患有先天性心脏病的婴儿有不同血小板亚群的改变,总体上聚集表型减少,分泌功能障碍。这些研究结果表明,患有先天性心脏病的婴儿体内的血小板可能因持续刺激而耗竭,这可能是与先天性心脏病相关的出血和血栓性血管并发症的原因。
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来源期刊
CiteScore
15.60
自引率
2.30%
发文量
337
审稿时长
2-4 weeks
期刊介绍: The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA). The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.
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