Impact of Food Exposome on Atherosclerotic Plaque Stability: Metabolomic Insights from Human Carotid Endarterectomy Specimen
Abstract
1. Introduction
2. Results
2.1. Patient and Plaque Characteristics Associated with Plaque Stability
2.2. Molecular Characteristics of Stability in Carotid Atherosclerotic Plaque
2.3. Metabolites Associated with Plaque Stability
2.4. Metabolites Associated with Plaque Vulnerability
2.5. Associations Between Metabolites Inside Plaque, Systemic Inflammation, and Lipid Profile
2.6. Metabolites of Mediterranean Diet and Plaque Stability
3. Discussion
Strengths and Limitations
4. Materials and Methods
4.1. Population and Clinico-Biological Data Collection
4.2. Collection and Preparation of Carotid Plaque for Metabolomic Analysis
4.3. Untargeted Metabolomic Analysis of Carotid Plaque
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AUC | Area Under the ROC curve |
BMI | Body Mass Index |
CRP | C-Reactive Protein |
CAS | Carotid Atherosclerotic Stenosis |
CEA | Carotid Endarterectomy |
DASH | Dietary Approaches to Stop Hypertension (DASH) |
ESI | Electrospray Ionization |
eGFR | estimated Glomerular Filtration rate by MDRD (Modification in Diet in Renal Disease) |
Col | high performance-liquid chromatography column used |
HDL-cholesterol | High-Density Lipoprotein cholesterol |
HMDB | Human Metabolome Database |
HILIC | Hydrophilic Interaction Liquid Chromatography |
IS | Ischemic stroke |
LC-MS | Liquid Chromatography coupled with tandem Mass Spectrometry |
LDL-cholesterol | Low-Density Lipoprotein cholesterol |
2PY | N-methyl-2-pyridone-5-carboxamide |
4PY | N1-methyl-4-pyridone-3-carboxamide |
NASCET | North American Symptomatic Carotid Endarterectomy Trial |
Px | Paraxanthine |
Pol | Polarity |
PAO | Polyamine Oxydase |
ROC | Receiver Operating Characteristic |
RT | Retention Time |
SSAT | Spermidine/Spermine n-Acetyltransferase |
SVM | Support Vector Machine |
Tb | Theobromine |
Tp | Theophylline |
TIA | Transient Ischemic Attack |
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All Patients | Asymptomatic Patients | Symptomatic Patients | p Value | |
---|---|---|---|---|
n = 72 | n = 42 | n = 30 | ||
Medical history before hospitalization | ||||
Age, y | 69.00 [63.75–77.00] | 70.00 [64.00–77.50] | 69.00 [63.25–76.75] | 0.833 |
Men | 56/72 (77.78%) | 31/42 (73.81%) | 25/30 (83.33%) | 0.338 |
High blood pressure | 53/72 (73.61%) | 32/42 (76.19%) | 21/30 (70.00%) | 0.557 |
Active smoker | 43/72 (59.72%) | 25/42 (59.52%) | 18/30 (60.00%) | 0.968 |
Diabetes mellitus | 26/72 (37.50%) | 19/42 (45.24%) | 8/30 (26.67%) | 0.109 |
Coronary disease | 22/72 (30.56%) | 15/42 (35.71%) | 7/30 (23.33%) | 0.261 |
BMI, kg/m2 | 25.61 [24.09–27.51] (3) | 25.48 [24.53–27.72] | 26.17 [23.78–27.22] (3) | 0.980 |
Obesity (BMI ≥ 30 kg/m2) | 12/69 (17.39%) | 9/42 (21.43%) | 3/27 (11.11%) | 0.270 |
Ischemic stroke or TIA | 12/72 (16.67%) | 5/42 (11.90%) | 7/30 (23.33%) | 0.201 |
Medical treatment before hospitalization | ||||
Antiplatelet therapy | 53/72 (73.61%) | 36/42 (85.71%) | 17/30 (56.67%) | 0.006 |
Lipid-lowering therapy | 43/72 (59.72%) | 32/42 (76.19%) | 11/30 (36.67%) | <0.001 |
Antidiabetes therapy | 23/72 (31.94%) | 16/42 (38.10%) | 7/30 (23.33%) | 0.185 |
Antihypertensive therapy | 55/72 (76.39%) | 33/42 (78.57%) | 22/30 (73.33%) | 0.606 |
CAS and CEA characteristics | ||||
NASCET measure of CAS, % | 77.50 [70.00–90.00] | 77.50 [70.00–90.00] | 77.50 [70.00–90.00] | 0.939 |
CEA under antiplatelet therapy | 67/72 (93.06%) | 39/42 (92.90%) | 28/30 (93.30%) | 0.938 |
Laboratory results at admission | ||||
Hemoglobin, g/dL | 13.55 [12.90–14.90] | 13.70 [12.93–14.98] | 13.35 [12.90–14.60] | 0.451 |
Hematocrit | 0.40 [0.38–0.44] | 0.40 [0.38–0.45] | 0.40 [0.37–0.43] | 0.457 |
Platelet count, G/L | 233.00 [209.00–291.75] | 231.50 [203.75–290.00] | 240.50 [214.25–288.25] | 0.421 |
Leukocyte count, G/L | 8.10 [6.59–9.30] (1) | 8.30 [6.95–9.45] | 7.92 [6.28–9.10] (1) | 0.261 |
C-reactive protein, mg/L | 2.40 [1.18–6.50] | 1.75 [0.73–4.65] | 3.90 [2.03–7.65] | 0.022 |
Fasting glycemia, g/L | 1.00 [0.86–1.19] (2) | 1.05 [0.87–1.35] (1) | 0.97 [0.86–1.12] (1) | 0.331 |
Total cholesterol, g/L | 1.58 [1.30–1.87] (6) | 1.60 [1.31–1.78] (4) | 1.55 [1.24–1.92] (2) | 0.979 |
LDL-cholesterol, g/L | 0.79 [0.56–1.04] (5) | 0.72 [0.50–0.91] (3) | 0.86 [0.66–1.16] (2) | 0.090 |
HDL-cholesterol, g/L | 0.43 [0.36–0.49] (5) | 0.46 [0.38–0.57] (3) | 0.39 [0.35–0.43] (2) | 0.010 |
Triglycerides, g/L | 1.23 [0.96–1.71] (5) | 1.25 [0.93–1.87] (3) | 1.20 [0.98–1.61] (2) | 0.809 |
Ratio of CRP to HDL-cholesterol | 5.68 [2.77–14.92] (5) | 4.00 [1.43–10.06] (3) | 10.46 [5.03–19.49] (2) | 0.004 |
eGRF, mL/min/1.73 m2 | 75.82 [58.25–93.43] | 63.72 [51.84–79.27] | 91.14 [76.07–98.93] | <0.001 |
Macroscopic description of the plaque after CEA | ||||
Calcified plaque | 17/72 (23.61%) | 14/42 (33.33%) | 3/30 (10.00%) | 0.022 |
Ulcerated plaque | 11/72 (15.28%) | 2/42 (4.76%) | 9/30 (30.00%) | 0.003 |
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Doche, E.; Leclercq, B.; Sulowski, C.; Magoncia, E.; Tardivel, C.; Svilar, L.; Sarlon-Bartoli, G.; Martin, J.-C.; Bartoli, M.; Rossillon, A.; et al. Impact of Food Exposome on Atherosclerotic Plaque Stability: Metabolomic Insights from Human Carotid Endarterectomy Specimen. Int. J. Mol. Sci. 2025, 26, 7018. https://doi.org/10.3390/ijms26147018
Doche E, Leclercq B, Sulowski C, Magoncia E, Tardivel C, Svilar L, Sarlon-Bartoli G, Martin J-C, Bartoli M, Rossillon A, et al. Impact of Food Exposome on Atherosclerotic Plaque Stability: Metabolomic Insights from Human Carotid Endarterectomy Specimen. International Journal of Molecular Sciences. 2025; 26(14):7018. https://doi.org/10.3390/ijms26147018
Chicago/Turabian StyleDoche, Emilie, Barbara Leclercq, Constance Sulowski, Ellen Magoncia, Catherine Tardivel, Ljubica Svilar, Gabrielle Sarlon-Bartoli, Jean-Charles Martin, Michel Bartoli, Alexandre Rossillon, and et al. 2025. "Impact of Food Exposome on Atherosclerotic Plaque Stability: Metabolomic Insights from Human Carotid Endarterectomy Specimen" International Journal of Molecular Sciences 26, no. 14: 7018. https://doi.org/10.3390/ijms26147018
APA StyleDoche, E., Leclercq, B., Sulowski, C., Magoncia, E., Tardivel, C., Svilar, L., Sarlon-Bartoli, G., Martin, J.-C., Bartoli, M., Rossillon, A., & Suissa, L. (2025). Impact of Food Exposome on Atherosclerotic Plaque Stability: Metabolomic Insights from Human Carotid Endarterectomy Specimen. International Journal of Molecular Sciences, 26(14), 7018. https://doi.org/10.3390/ijms26147018