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DOI: 10.1055/s-0043-57017
Platelet-Released Extracellular Vesicle Characteristics Differ in Chronic and in Acute Heart Disease
Funding This work was supported by the Spanish Society of Cardiology [“SEC-2016” to L.B.; “Investigación Clínica 2017” to A.C.]; Spanish Ministry of Economy and Competitiveness of Science “Agencia Estatal de Investigación (AEI)” Proj Ref AEI / 10.13039/501100011033-[PID2019-107160RB-I00] to L.B.; Institute of Health Carlos III (ISCIII) [Red RICORS TERAV- RD21/0017/0013 to L.B.; FIS PI19/01687 to T.P.]; CIBERCV to L.B. and A.C., Sociedad Valenciana de Cardiología 2017 to A.C.; and cofounded by FEDER “Una Manera de Hacer Europa.” We thank Fundación Jesus Serra and Fundación de Investigación Cardiovascular (Barcelona, Spain) for their continuous support. A.V.-F. and N.M.-G. are the recipients of a research contract from the Cardiovascular Program-ICCC (IR-HSCSP). R.S. is the recipient of a Beatriu de Pinós Fellowship [2019BP00211] from the University and Research Grants Management Agency (Government of Catalonia) co-funded by COFUND-Marie Skłodowska-Curie Actions in the Horizon 2020 program (European Commission, contract number 801370).
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 (n = 119), ACS patients (n = 58), their respective controls (non-CHF [n = 21] and non-ACS [n = 24], respectively), and a reference control group (n = 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 αIIb-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.
Keywords
acute coronary syndrome - chronic heart failure - extracellular vesicles - phosphatidylserine - platelet-derived extracellular vesiclesAuthors' Contribution
L.B., T.P., S.M., and A.C. designed the research. A.V.-F. performed experiments. A.V.-F., T.P., and L.B. analyzed the results. A.V.-F., N.M.-G., A.C., R.S., S.M., T.P., and L.B. wrote and revised the manuscript.
Publication History
Received: 01 December 2022
Accepted: 14 March 2023
Article published online:
19 April 2023
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