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血小板释放的细胞外囊泡特征在慢性和急性心脏病中存在差异。

Platelet-Released Extracellular Vesicle Characteristics Differ in Chronic and in Acute Heart Disease.

机构信息

Cardiovascular Program-ICCC, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain.

Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Spain.

出版信息

Thromb Haemost. 2023 Sep;123(9):892-903. doi: 10.1055/s-0043-57017. Epub 2023 Apr 19.

Abstract

BACKGROUND

Extracellular vesicles (EVs), shed in response to cell activation, stress, or injury, are increased in the blood of patients with cardiovascular disease. EVs are characterized by expressing parental-cell antigens, allowing the determination of their cellular origin. Platelet-derived EVs (pEVs) are the most abundant in blood. Although not universally given, EVs generally express phosphatidylserine (PS) in their membrane.

OBJECTIVES

To investigate pEVs in chronic and acute conditions, such as chronic heart failure (CHF) and first-onset acute coronary syndrome (ACS), in patients treated as per guidelines.

METHODS

EVs in CHF patients ( = 119), ACS patients ( = 58), their respective controls (non-CHF [ = 21] and non-ACS [ = 24], respectively), and a reference control group ( = 31) were characterized and quantified by flow cytometry, using monoclonal antibodies against platelet antigens, and annexin V (AV) to determine PS exposure.

RESULTS

CHF patients had higher EVs-PS numbers, while ACS had predominantly EVs-PS. In contrast to ACS, CHF patients had significantly reduced numbers of pEVs carrying PECAM and α-integrin epitopes (CD31/AV, CD41a/AV, and CD31/CD41a/AV), while no differences were observed in P-selectin-rich pEVs (CD62P/AV) compared with controls. Additionally, background etiology of CHF (ischemic vs. nonischemic) or ACS type (ST-elevation myocardial infarction [STEMI] vs. non-STEMI [NSTEMI]) did not affect pEV levels.

CONCLUSION

PS exposure in EV and pEV-release differ between CHF and ACS patients, with tentatively different functional capacities beyond coagulation to inflammation and cross-talk with other cell types.

摘要

背景

细胞外囊泡(EVs)在细胞激活、应激或损伤时释放,在心血管疾病患者的血液中增加。EVs 的特征在于表达亲代细胞抗原,从而能够确定其细胞来源。血小板衍生的 EVs(pEVs)在血液中最为丰富。尽管并非普遍存在,但 EVs 的膜通常表达磷脂酰丝氨酸(PS)。

目的

在接受指南治疗的慢性心力衰竭(CHF)和首次发作的急性冠状动脉综合征(ACS)等慢性和急性情况下,研究 pEVs。

方法

通过流式细胞术,使用针对血小板抗原的单克隆抗体和 Annexin V(AV)来确定 PS 暴露,对 CHF 患者(n=119)、ACS 患者(n=58)、各自的对照者(非 CHF [n=21] 和非 ACS [n=24])和参考对照组(n=31)的 EVs 进行特征和定量分析。

结果

CHF 患者的 EVs-PS 数量较高,而 ACS 患者则主要具有 EVs-PS。与 ACS 不同,CHF 患者携带 PECAM 和 α 整合素表位(CD31/AV、CD41a/AV 和 CD31/CD41a/AV)的 pEVs 数量显著减少,而与对照组相比,富含 P-选择素的 pEVs(CD62P/AV)没有差异。此外,CHF 的背景病因(缺血性与非缺血性)或 ACS 类型(ST 段抬高型心肌梗死 [STEMI] 与非 STEMI [NSTEMI])并不影响 pEV 水平。

结论

CHF 和 ACS 患者之间 EV 和 pEV 释放的 PS 暴露不同,具有潜在不同的功能能力,超出了凝血至炎症以及与其他细胞类型的相互作用。

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