Circulating MicroRNA Levels Indicate Platelet and Leukocyte Activation in Endotoxemia Despite Platelet P2Y(12) Inhibition

Fecha de publicación: 01/04/2020 Fecha Ahead of Print: 21/04/2020

Autores de IIS La Fe

Aitana Braza Boils

Autor

Participantes ajenos a IIS La Fe

Barwari, T
Gutmann, C
Thomas, MR
Judge, HM
Joshi, A
Pechlaner, R
Shankar-Hari, M
Ajjan, RA
Sabroe, I
Storey, RF
Mayr, M

Grupos

Cardiopatías familiares, muerte súbita y mecanismos de enfermedad (CAFAMUSME)

Investigador Principal

Aitana Braza Boils

Abstract

There is evidence for the effects of platelet inhibition on innate immune activation. Circulating microRNAs (miRNAs) have been implicated as markers of platelet and leukocyte activation. In the present study, we assessed the effects of P2Y(12) inhibitors on platelet and leukocyte miRNAs during endotoxemia. Healthy volunteers were randomly assigned to receive oral ticagrelor (n = 10), clopidogrel (n = 8) or no drug (n = 8) for one week, followed by an intravenous bolus of 2 ng/kg endotoxin. Serum was collected at baseline, after one week of antiplatelet treatment and 6 and 24 h after endotoxin administration. MiRNAs were screened using LNA-based qPCR, followed by TaqMan-qPCR validation of candidates. Clinical validation was performed in 41 sepsis patients. Platelet-enriched miR-197, miR-223 and miR-223* were decreased in volunteers following antiplatelet therapy. Endotoxin increased platelet miRNAs, whilst the opposite effect was seen for leukocyte-enriched miR-150. Neither of these endotoxin-mediated effects were altered by P2Y(12) inhibitors. Sepsis patients with fatal outcomes (n = 12) had reduced miR-150 levels compared with survivors (n = 29). In conclusion, we show that miR-150 is downregulated in experimental endotoxemia and can predict survival in sepsis but is unaffected by P2Y(12) inhibition. While P2Y(12) inhibition reduces platelet-associated miRNAs in healthy volunteers, it fails to attenuate the response of platelet miRNAs to endotoxemia.

Datos de la publicación

ISSN/ISSNe:: 1661-6596, 1661-6596
Tipo:: Article
Páginas:: -
DOI:: 10.3390/ijms21082897
Factor de Impacto:: 1,455 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Braza-Boils, A:: Kings Coll London, Kings British Heart Fdn Ctr, London SE5 9NU, England

Instituto de Investigación. Hlth Res Inst La Fe, Valencia 46026, Spain
Barwari, T:: Kings Coll London, Kings British Heart Fdn Ctr, London SE5 9NU, England
Gutmann, C:: Kings Coll London, Kings British Heart Fdn Ctr, London SE5 9NU, England
Thomas, MR:: Univ Birmingham, Inst Cardiovasc Sci, Birmingham B15 2TT, W Midlands, England
Judge, HM:: Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield S10 2RX, S Yorkshire, England
Joshi, A:: Kings Coll London, Kings British Heart Fdn Ctr, London SE5 9NU, England
Pechlaner, R:: Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria
Shankar-Hari, M:: Guys & St Thomas NHS Fdn Trust, Crit Care Med, London SE1 7EH, England
Ajjan, RA:: Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds LS2 9JT, W Yorkshire, England
Sabroe, I:: Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield S10 2RX, S Yorkshire, England
Storey, RF:: Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield S10 2RX, S Yorkshire, England
Mayr, M:: Kings Coll London, Kings British Heart Fdn Ctr, London SE5 9NU, England

Keywords

biomarker; microRNA; antiplatelet therapy; sepsis

Proyectos asociados

RED INVESTIGACION (RECAVA)

RD06/0014/0004 . INSTITUTO DE SALUD CARLOS III; FUNDACION PARA LA INV BIOMEDICA- HOSPITAL GREGORIO MARAÑON; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2006