Enhanced prothrombotic and proinflammatory activity of circulating extracellular vesicles in acute exacerbations of chronic obstructive pulmonary disease

被引:6
作者
Nieri, Dario [1 ,2 ]
Morani, Camilla [1 ,2 ]
De Francesco, Miriam [1 ,2 ]
Gaeta, Roberta [1 ,2 ]
Niceforo, Mariapia [1 ,2 ]
De Santis, Mariella [3 ]
Giusti, Ilaria [4 ]
Dolo, Vincenza [4 ]
Daniele, Marta [5 ,8 ]
Papi, Alberto [5 ]
Celi, Alessandro [1 ,2 ,6 ,7 ]
Neri, Tommaso [2 ,6 ]
机构
[1] Azienda Osped Univ Pisana, UO Pneumol, Pisa, Italy
[2] Univ Pisa, Dipartimento Patol Chirurg Med Mol & Area Crit, Pisa, Italy
[3] Azienda Osped Univ Pisana, Dipartimento CardioToracoVasc, Pisa, Italy
[4] Univ Aquila, Dept Life Hlth & Environm Sci, Laquila, Italy
[5] Univ Ferrara, Dept Med Sci, Ctr Asthma & COPD, Ferrara, Italy
[6] Univ Pisa, Ctr Dipartimentale Biol Cellulare Cardioresp, Pisa, Italy
[7] Univ Pisa, Dipartimento Patol Chirurg Med Mol & Area Crit, Direz Area Med, Via Savi 8, I-56124 Pisa, Italy
[8] ULSS5 Polesana, UOC Pneumol, Rovigo, Italy
关键词
Extracellular vesicles; Thrombosis; Inflammation; Chronic obstructive pulmonary disease; Cardiovascular risk; BRONCHOALVEOLAR LAVAGE FLUID; SYSTEMIC INFLAMMATION; TISSUE FACTOR; MICROPARTICLES; EXOSOMES; CELLS; COPD;
D O I
10.1016/j.rmed.2024.107563
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are associated with a high rate of cardiovascular events. Thromboinflammation (the interplay between coagulation and inflammation) is probably involved in these events. Extracellular vesicles (EV) increase during AE-COPD, but their role in thromboinflammation in COPD is still unknown. We investigated EV-associated prothrombotic and proinflammatory activity in COPD. Methods: Patients with AE-COPD, stable COPD (sCOPD) and age- and sex-matched subjects (controls) were enrolled. AE-COPD patients were evaluated at hospital admission and 8 weeks after discharge (recovery; longitudinal arm). In a cross-sectional arm, AE-COPD were compared with sCOPD and controls. EV-mediated prothrombotic activity was tested by measuring the concentration of EV-associated phosphatidylserine, as assessed by a prothrombinase assay, and tissue factor, as assessed by a modified one-stage clotting assay (EV-PS and EV-TF, respectively). Synthesis of interleukin-8 (IL-8) and C-C motif chemokine ligand-2 (CCL2) by cells of the human bronchial epithelial cell line 16HBE incubated with patients' EV was used to measure EV-mediated proinflammatory activity. Results: Twenty-five AE-COPD (median age [interquartile range] 74.0 [14.0] years), 31 sCOPD (75.0 [9.5] years) and 12 control (67.0 [3.5] years) subjects were enrolled. In the longitudinal arm, EV-PS, EV-TF, IL-8 and CCL-2 levels were all significantly higher at hospital admission than at recovery. Similarly, in the cross-sectional arm, EV-PS, EV-TF and cytokines synthesis were significantly higher in AE-COPD than in sCOPD and controls. Conclusions: EV exert prothrombotic and proinflammatory activities during AE-COPD and may therefore be effectors of thromboinflammation, thus contributing to the higher cardiovascular risk in AE-COPD.
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页数:7
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