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

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 α_IIb-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 vesicles

Authors' 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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