Functional Impairment of Endothelial Colony Forming Cells (ECFC) in Patients with Severe Atherosclerotic Cardiovascular Disease (ASCVD)
Abstract
:1. Introduction
2. Results
2.1. Characteristics of the Population
2.2. Characterization of EPCs in Patients with ASCVD
2.3. ECFC Functionality According to the ASCVD Presence and Severity
2.4. Associations between PC Subpopulations Counts and Functionality, Arterial Phenotypes, and Circulating Markers
3. Discussion
4. Materials and Methods
4.1. Subjects
4.2. Cells Characterization
4.3. Enumeration and Characterization of Circulating Progenitor Cells by Flow Cytometry
4.4. Assessment of Colony-Forming Unit-Endothelial Cells
4.5. Assessment of Endothelial Colony Forming Cells
4.6. ECFC Functional Tests (Proliferation, Senescence, and Vasculogenic Properties)
4.7. IL-6 and VEGF Plasmatic Levels Determination
4.8. Characterization of Arterial Phenotype
4.8.1. Carotid Femoral Pulse Wave Velocity (PWV)
4.8.2. Carotid Artery Intima-Media Thickness (IMT) and Presence of Carotid Atherosclerotic Plaque
4.9. Measurement of Blood Pressure
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
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All Participants | N | ASCVD | ||||
---|---|---|---|---|---|---|
No | N | Yes | N | |||
Gender (women%) | 35% | 243 | 52% | 124 | 17% *** | 119 |
Age (years) | 62 ± 14 | 243 | 57 ± 16 | 124 | 68 ± 10 *** | 119 |
BMI (kg/m2) | 26.9 ± 6.1 | 240 | 27.0 ± 5.8 | 124 | 26.8 ± 6.4 | 116 |
ASCVD sites | ||||||
Coronary | 24% | 243 | - | 124 | 49% | 119 |
Carotido-cerebral | 16% | 243 | - | 124 | 32% | 119 |
Femoro-popliteal | 23% | 243 | - | 124 | 47% | 119 |
Others | 2% | 243 | - | 124 | 3% | 119 |
Number of ASCVD sites | 0.64 ± 0.74 | 243 | - | 124 | 1.31 ± 0.50 | 119 |
ACSVD | 49% | 243 | - | 124 | 100% | 119 |
ASCVD Risk factors | ||||||
Hypertension | 45% | 242 | 34% | 123 | 57% *** | 119 |
Diabetes | 18% | 242 | 10% | 123 | 27% *** | 119 |
Dyslipidaemia | 23% | 242 | 12% | 123 | 34% *** | 119 |
Smoking | 50% | 242 | 29% | 123 | 71% *** | 119 |
Treatments | ||||||
Anti-hypertensive drugs | 59% | 243 | 40% | 124 | 79% *** | 119 |
Anti-diabetic drugs | 15% | 243 | 7% | 124 | 24% *** | 119 |
Anti-coagulant drugs | 12% | 243 | 7% | 124 | 17% * | 119 |
Statins | 41% | 243 | 15% | 124 | 68% *** | 119 |
Number of CV and metabolic drugs | 2.9 ± 2.7 | 243 | 1.4 ± 1.9 | 124 | 4.4 ± 2.5 *** | 119 |
Total number of drugs | 3.1 ± 2.8 | 243 | 1.6 ± 2.0 | 124 | 4.7 ± 2.6 *** | 119 |
Blood pressure | ||||||
SBP (mmHg) | 135 ± 18 | 179 | 133 ± 17 | 95 | 136 ± 20 | 84 |
DBP (mmHg) | 76 ± 10 | 179 | 78 ± 10 | 95 | 74 ± 10 ** | 84 |
MBP (mmHg) | 95 ± 11 | 179 | 96 ± 11 | 95 | 94 ± 11 | 84 |
PP (mmHg) | 59 ± 16 | 179 | 55 ± 14 | 95 | 63 ± 17 ** | 84 |
HR (bpm) | 73 ± 14 | 179 | 75 ± 13 | 95 | 72 ± 15 | 84 |
Arterial phenotypes | ||||||
PWV (m/s) | 12.30 ± 2.74 | 169 | 11.77 ± 2.50 | 89 | 12.88 ± 2.89 * | 80 |
Carotid thickness (mm) | 0.79 ± 0.18 | 129 | 0.74 ± 0.18 | 71 | 0.85 ± 0.15 *** | 58 |
Carotid plaque presence | 65% | 127 | 51% | 69 | 83% *** | 58 |
Plasmatic markers | ||||||
IL-6 (pg/mL) | 1.90 (0.95–4.78) | 237 | 1.16 (0.71–2.76) | 120 | 3.13 (1.36–6.48) *** | 117 |
VEGF (pg/mL) | 15.7 (10.1–27.0) | 237 | 17.3 (12.26–30.89) | 120 | 14.06 (7.32–23.08) *** | 117 |
(A) | All Participants | N | ASCVD | p | |||
No | N | Yes | N | ||||
CD34+ cells (/mL) | 1324 (802–2023) | 240 | 1338 (880–2032) | 122 | 1297 (722–2021) | 118 | 0.75 |
CD45+CD34+KDR+ (/mL) | 8.09 (0–24.85) | 84 | 0 (0–20.56) | 33 | 13.68 (0–31.84) | 51 | 0.02 |
CFU-EC (/million cells) | 0.49 (0–3.45) | 220 | 0.40 (0–3.27) | 112 | 0.51 (0–3.80) | 108 | 0.68 |
(B) | Number of ASCVD Sites | Trend p | |||||
0 | N | 1 | N | >2 | N | ||
CD34+ cells (/mL) | 1338 (880–2032) | 122 | 1256 (701–2025) | 83 | 1423 (1036–1846) | 35 | 0.93 |
CD45+CD34+KDR+ (/mL) | 0 (0–20.56) | 33 | 11.56 (0–23.53) | 32 | 22.79 (5.55–37.70) | 19 | 0.004 |
CFU-EC (/million cells) | 0.40 (0–3.27) | 112 | 0.20 (0–3.06) | 75 | 1.29 (0–9.99) | 33 | 0.33 |
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Simoncini, S.; Toupance, S.; Labat, C.; Gautier, S.; Dumoulin, C.; Arnaud, L.; Stathopoulou, M.G.; Visvikis-Siest, S.; Rossi, P.M.; Benetos, A.; et al. Functional Impairment of Endothelial Colony Forming Cells (ECFC) in Patients with Severe Atherosclerotic Cardiovascular Disease (ASCVD). Int. J. Mol. Sci. 2022, 23, 8969. https://doi.org/10.3390/ijms23168969
Simoncini S, Toupance S, Labat C, Gautier S, Dumoulin C, Arnaud L, Stathopoulou MG, Visvikis-Siest S, Rossi PM, Benetos A, et al. Functional Impairment of Endothelial Colony Forming Cells (ECFC) in Patients with Severe Atherosclerotic Cardiovascular Disease (ASCVD). International Journal of Molecular Sciences. 2022; 23(16):8969. https://doi.org/10.3390/ijms23168969
Chicago/Turabian StyleSimoncini, Stéphanie, Simon Toupance, Carlos Labat, Sylvie Gautier, Chloé Dumoulin, Laurent Arnaud, Maria G. Stathopoulou, Sophie Visvikis-Siest, Pascal M. Rossi, Athanase Benetos, and et al. 2022. "Functional Impairment of Endothelial Colony Forming Cells (ECFC) in Patients with Severe Atherosclerotic Cardiovascular Disease (ASCVD)" International Journal of Molecular Sciences 23, no. 16: 8969. https://doi.org/10.3390/ijms23168969