Dietary Nitrate Supplementation Reduces Circulating Platelet-Derived Extracellular Vesicles in Coronary Artery Disease Patients on Clopidogrel Therapy: A Randomised, Double-Blind, Placebo-Controlled Study
Burnley-Hall N, Abdul F, Androshchuk V, Morris K, Ossei-Gerning N, Anderson R, Rees DA, James PE
Thrombosis and haemostasis · 14 citas
Etiquetas de revisión
Solo mecanismosDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Solo mecanismos
- Consumo medido con
- No se indica
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- Health and Care Research Wales
- Subvenciones
- Health and Care Research Wales (HS-14-08)
Según 1 financiador declarado.
Publicación
- Publicado
- 2018-01-01 · Thromb Haemost · vol. 118 · número 01 · págs. 112–122
- Editorial
- Thieme Medical Publishers (Germany)
- Citado
- 19 citas · más que el 68% de estudios similares · 0.8× el promedio de su campo
- Referencias
- 50 trabajos
- Acceso
- De pago
- Áreas de investigación
- Extracellular vesicles in disease · Antiplatelet Therapy and Cardiovascular Diseases · Nitric Oxide and Endothelin Effects
- Palabras clave
- dietary nitrate, nitrate supplementation, platelet-derived extracellular vesicles, coronary artery disease, clopidogrel, S-nitrosothiols, nitric oxide bioavailability, platelet activation, platelet aggregation, thrombin generation, cardiovascular risk, nanoparticle tracking analysis
- MeSH
- blood platelets, humans, nitrates, nitrites, ozone, s-nitrosothiols, cross-over studies, double-blind method, inhibitory concentration 50, platelet aggregation, hydrogen-ion concentration, dietary supplements, aged, middle aged, female, male, luminescence, coronary artery disease, extracellular vesicles, clopidogrel
8 autores
- Nicholas Burnley-Hall🇬🇧Cardiff University
- Fairoz Belary Abdul🇬🇧Cardiff University
- Vitaliy Androshchuk🇬🇧Cardiff University
- Keith Morris🇬🇧Cardiff Metropolitan University
- Nick Ossei‐Gerning🇬🇧University Hospital of Wales
- Richard Anthony Anderson🇬🇧University Hospital of Wales
- Aled Rees🇬🇧Cardiff University
- Philip Eurig James🇬🇧 · autor de correspondenciaCardiff Metropolitan University
Resumen
El texto original del estudio, en el idioma en que se publicó.
Extracellular vesicles (EVs) are implicated in the pathogenesis of cardiovascular disease (CVD). Specifically, platelet-derived EVs are highly pro-coagulant, promoting thrombin generation and fibrin clot formation. Nitrate supplementation exerts beneficial effects in CVD, via an increase in nitric oxide (NO) bioavailability. Clopidogrel is capable of producing NO-donating compounds, such as S-nitrosothiols (RSNO) in the presence of nitrite and low pH. The aim of this study was to assess the effect of nitrate supplementation with versus without clopidogrel therapy on circulating EVs in coronary artery disease (CAD) patients. In this randomized, double-blind, placebo-controlled study, CAD patients with (n = 10) or without (n = 10) clopidogrel therapy received a dietary nitrate supplement (SiS nitrate gel) or identical placebo. NO metabolites and platelet activation were measured using ozone-based chemiluminescence and multiple electrode aggregometry. EV concentration and origin were determined using nanoparticle tracking analysis and time-resolved fluorescence. Following nitrate supplementation, plasma RSNO was elevated (4.7 ± 0.8 vs 0.2 ± 0.5 nM) and thrombin-receptor mediated platelet aggregation was reduced (-19.9 ± 6.0 vs 4.0 ± 6.4 U) only in the clopidogrel group compared with placebo. Circulating EVs were significantly reduced in this group (-1.183e11 ± 3.15e10 vs -9.93e9 ± 1.84e10 EVs/mL), specifically the proportion of CD41+ EVs (-2,120 ± 728 vs 235 ± 436 RFU [relative fluorescence unit]) compared with placebo. In vitro experiments demonstrated clopidogrel-SNO can reduce platelet-EV directly (6.209e10 ± 4.074e9 vs 3.94e11 ± 1.91e10 EVs/mL). In conclusion, nitrate supplementation reduces platelet-derived EVs in CAD patients on clopidogrel therapy, increasing patient responsiveness to clopidogrel. Nitrate supplementation may represent a novel approach to moderating the risk of thrombus formation in CAD patients.
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