Plasma Instead of Serum Avoids Critical Confounding of Clinical Metabolomics Studies by Platelets

Metabolomics is an emerging and powerful bioanalytical method supporting clinical investigations. Serum and plasma are commonly used without rational prioritization. Serum is collected after blood coagulation, a complex biochemical process involving active platelet metabolism. This may affect the metabolome and increase the variance, as platelet counts and function may vary substantially in individuals. A multiomics approach systematically investigating the suitability of serum and plasma for clinical studies demonstrated that metabolites correlated well (n = 461, R2 = 0.991), whereas lipid mediators (n = 83, R2 = 0.906) and proteins (n = 322, R2 = 0.860) differed substantially between specimen. Independently, analysis of platelet releasates identified most biomolecules significantly enriched in serum compared to plasma. A prospective, randomized, controlled parallel group metabolomics trial with acetylsalicylic acid administered for 7 days demonstrated that the apparent drug effects significantly differ depending on the analyzed specimen. Only serum analyses of healthy individuals suggested a significant downregulation of TXB2 and 12-HETE, which were specifically formed during coagulation in vitro. Plasma analyses reliably identified acetylsalicylic acid effects on metabolites and lipids occurring in vivo such as an increase in serotonin, 15-deoxy-PGJ2 and sphingosine-1-phosphate and a decrease in polyunsaturated fatty acids. The present data suggest that plasma should be preferred above serum for clinical metabolomics studies as the serum metabolome may be substantially confounded by platelets.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Journal of proteome research - (2024) vom: 23. März

Sprache:

Englisch

Beteiligte Personen:

Hagn, Gerhard [VerfasserIn]
Meier-Menches, Samuel M [VerfasserIn]
Plessl-Walder, Günter [VerfasserIn]
Mitra, Gaurav [VerfasserIn]
Mohr, Thomas [VerfasserIn]
Preindl, Karin [VerfasserIn]
Schlatter, Andreas [VerfasserIn]
Schmidl, Doreen [VerfasserIn]
Gerner, Christopher [VerfasserIn]
Garhöfer, Gerhard [VerfasserIn]
Bileck, Andrea [VerfasserIn]

Links:

Volltext

Themen:

Acetylsalicylic acid
Clinical metabolomics
Confounders
Drug effects
Journal Article
Lipid mediators
Metabolomics
Omega-3 fatty acids
Plasma
Platelets
Serum

Anmerkungen:

Date Revised 23.03.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1021/acs.jproteome.3c00761

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370102398