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LC-MS Analysis of Human Platelets as a Platform for Studying Mitochondrial Metabolism
Published on: April 4, 2016
Metabolomic Analysis of Platelets of Patients With Aspirin Non-Response
Jiun-Yang Chiang1,2, Sheng-Han Lee3, Yen-Ching Chen4
1Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Insights
Platelet metabolomes did not differ between aspirin non-responders and responders. Lower glycine levels may be linked to increased platelet activity in younger patients, suggesting a role in aspirin resistance.
Area of Science:
- Cardiovascular Medicine
- Metabolomics
- Pharmacogenomics
Background:
- Aspirin is a primary antiplatelet agent for cardiovascular disease prevention.
- A significant portion of patients exhibit aspirin non-response, with underlying mechanisms unclear.
- Platelet metabolomic differences may contribute to aspirin resistance in coronary artery disease (CAD).
Purpose of the Study:
- To investigate hydrophilic platelet metabolite profiles in aspirin non-responders versus responders with CAD.
- To identify potential metabolic biomarkers associated with aspirin resistance.
Main Methods:
- Collected platelet samples from 29 aspirin non-responders and 31 responders with CAD.
- Analyzed hydrophilic metabolites using nuclear magnetic resonance (NMR) spectroscopy.
- Applied multivariate statistical analysis, including partial least squares discriminant analysis (PLS-DA).
Main Results:
- No significant differences in overall hydrophilic platelet metabolic profiles were found between responders and non-responders.
- Lower serum glycine levels were associated with shorter platelet aggregation times, but this finding was not statistically significant after multiple testing correction.
- PLS-DA models could not differentiate between the two groups based on metabolic profiles.
Conclusions:
- Platelet hydrophilic metabolomes do not appear to differ between aspirin non-responders and responders.
- Lower glycine levels may play a role in aspirin non-response, particularly in patients under 65 years old.
- Further research is needed to elucidate the role of glycine in aspirin resistance pathophysiology.
Abstract:
Background: Aspirin is the most commonly used antiplatelet agent for the prevention of cardiovascular diseases. However, a certain proportion of patients do not respond to aspirin therapy. The mechanisms of aspirin non-response remain unknown. The unique metabolomes in platelets of patients with coronary artery disease (CAD) with aspirin non-response may be one of the causes of aspirin resistance. Materials and Methods: We enrolled 29 patients with CAD who were aspirin non-responders, defined as a study subject who were taking aspirin with a platelet aggregation time less than 193 s by PFA-100, and 31 age- and sex-matched patients with CAD who were responders. All subjects had been taking 100 mg of aspirin per day for more than 1 month. Hydrophilic metabolites from the platelet samples were extracted and analyzed by nuclear magnetic resonance (NMR). Both 1D 1H and 2D J-resolved NMR spectra were obtained followed by spectral processing and multivariate statistical analysis, such as partial least squares discriminant analysis (PLS-DA). Results: Eleven metabolites were identified. The PLS-DA model could not distinguish aspirin non-responders from responders. Those with low serum glycine level had significantly shorter platelet aggregation time (mean, 175.0 s) compared with those with high serum glycine level (259.5 s). However, this association became non-significant after correction for multiple tests. Conclusions: The hydrophilic metabolic profile of platelets was not different between aspirin non-responders and responders. An association between lower glycine levels and higher platelet activity in patients younger than 65 years suggests an important role of glycine in the pathophysiology of aspirin non-response.

