The Value of SIRT1/FOXO1 Signaling Pathway in Early Detection of Cardiovascular Risk in Children with β-Thalassemia Major
Abstract
:1. Introduction
2. Materials and Methods
2.1. Inclusion and Exclusion Criteria
2.2. Echocardiography
2.2.1. Carotid Intima-Media Thickness (CIMT)
2.2.2. Arterial Carotid Beta Stiffness (β Index)
2.3. Blood Sample Collection
2.4. Biochemical Assessment
2.4.1. Assessment of SIRT1, FOXO1, Hepcidin, and HSP72
2.4.2. Assessment of Redox Status Parameters
2.4.3. Determination of FOXO1 Gene Expression
2.5. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameters | Groups | ANOVA | ||||
---|---|---|---|---|---|---|
Group I (n = 50) Control | Group II (n = 50) CIMT ≤ 0.5 mm | Group III (n = 50) CIMT > 0.5 mm | F | p-value | ||
Age | Range | 6–13 | 6–12 | 6–14 | 0.384 | 0.682 (ns) |
Mean ± SD | 8.700 ± 1.799 | 8.840 ± 1.777 | 8.850 ± 1.911 | |||
BMI (kg/m2) | Range | 18.5–23.6 | 18.6–24 | 23–26.5 | 153.943 | <0.001 * |
Mean ± SD | 20.908 ± 1.682 | 21.222 ± 1.646 * | 25.5 ± 0.712 *# | |||
CIMT (mm) | Range | 0.20–0.39 | 0.24–0.48 | 0.51–1.10 | 296.486 | <0.001 * |
Mean ± SD | 0.278 ± 0.057 | 0.380 ± 0.054 * | 0.774 ± 0.169 *# | |||
Beta stiffness | Range | 2–2.6 | 3–3.7 | 4–4.6 | 668.952 | <0.001 * |
Mean ± SD | 2.316 ± 0.162 | 3.418 ± 0.172 * | 4.278 ± 0.1345 *# | |||
Ferritin (ng/dl) | Range | 28–165 | 1450–7655 | 1655–7800 | 209.315 | <0.001 * |
Mean ± SD | 60.94 ± 29.860 | 4327.32 ±1397.42 * | 4570.88 ± 1629.94 *# | |||
AIP | Range | 0.11–0.30 | 0.15–0.35 | 0.46–0.63 | 720.547 | <0.001 * |
Mean ± SD | 0.219 ±0.050 | 0.277 ± 0.047 * | 0.552 ± 0.043 *# | |||
SIRT1 (ng/mL) | Range | 2.5–4 | 1.5–3 | 0.5–1.9 | 278.359 | <0.001 * |
Mean ± SD | 3.17 ± 0.53 | 2.175 ± 0.358 * | 1.145 ± 0.371 *# | |||
ANP (pg/mL) | Range | 25–67 | 60–98 | 105–126 | 552.919 | <0.001 * |
Mean ± SD | 44.12 ± 13.17 | 75.34 ± 11.19 * | 113.66 ± 5.42 *# | |||
CPK MB (U/L) | Range | 25–126 | 28–132 | 29–140 | 0.040 | <0.961 |
Mean ± SD | 59.24 ± 26.99 | 59.5 ± 26.99 | 60.78 ± 33.41 | |||
LDH1 (U/L) | Range | 160–200 | 180- 240 | 210–280 | 434.376 | <0.001 * |
Mean ± SD | 179.38 ±10.016 | 222.8 ± 12.378 * | 258.32 ± 16.918 *# | |||
Hepcidin (ng/mL) | Range | 33–42 | 18–25 | 13–15 | 1735.039 | < 0.001 * |
Mean ± SD | 37.40 ± 3.024 | 22.30 ± 1.555 * | 13.958 ± 0.803 *# | |||
HSP72 (ng/L) | Range | 25.20–36.15 | 48.07–184.86 | 50.73–200.65 | 57.608 | <0.001 * |
Mean ± SD | 30.128 ± 3.562 | 92.349 ± 42.561 * | 105.845 ± 49.223 *# | |||
SOD (U/L) | Range | 6.5–8.5 | 5.6–7 | 3–4.25 | 1111.727 | <0.001 * |
Mean ± SD | 7.48 ± 0.572 | 6.51 ± 0.428 * | 3.50 ± 0.263 *# | |||
Catalase (U/L) | Range | 32–35 | 29–33.2 | 11.5–13.6 | 8836.11 | <0.001 * |
Mean ± SD | 33.614 ± 0.989 | 30.046 ± 0.962 * | 12.398 ± 0.540 *# | |||
MDA (Nmol/mL) | Range | 1.25–3.5 | 4–8.1 | 5.5–8.54 | 464.527 | <0.001 * |
Mean ± SD | 2.236 ± 0.75 | 6.258 ± 1.047 * | 7.365 ± 0.832 *# | |||
FOXO1 (Ng/mL) | Range | 3–4.9 | 6–8.3 | 8.5–15.7 | 1541.81 | <0.001 * |
Mean ± SD | 3.436 ± 0.489 | 7.22 ± 0.704 * | 12.76 ± 1.184 *# | |||
FOXO1 relative gene expression | Range | 0.8–1.9 | 0.9–2.23 | 2.3–3.4 | 496.654 | <0.001 * |
Mean ± SD | 1.155 ± 0.226 | 1.725 ± 0.277 * | 2.702 ± 0.239 *# |
Pearson’s Correlations | Partial Correlation Coefficient | |||
---|---|---|---|---|
CIMT (mm) | ||||
r | p-Value | r′ | p-Value | |
BMI | 0.716 | <0.001 * | −0.019 | 0.829 |
AIP | 0.851 | <0.001 * | 0.095 | 0.270 |
Hepcidin (ng/mL) | −0.589 | <0.001 * | 0.062 | 0.470 |
ANP (pg/mL) | 0.825 | <0.001 * | 0.079 | 0.355 |
CPK MB (U/L) | −0.013 | 0.875 | −0.150 | 0.078 |
LDH1 (U/L) | 0.765 | <0.001 * | −0.039 | 0.646 |
Hsp72 (ng/mL) | 0.365 | <0.001 * | −0.306 | <0.001 * |
SIRT1(ng/ml) | −0.760 | <0.001 * | 0.023 | 0.798 |
SOD (U/L) | −0.863 | <0.001 * | −0.047 | 0.583 |
Catalase (U/L) | −0.887 | <0.001 * | −0.106 | 0.216 |
MDA (Nmol/mL) | 0.660 | <0.001 * | 0.014 | 0.869 |
FOXO1 (ng/mL) | 0.876 | <0.001 * | 0.282 | 0.001 * |
FOXO1 relative gene expression | 0.835 | <0.001 * | 0.097 | 0.256 |
Variables | Unstandardized Estimate Parameter | β | Standardized Estimate Parameters | 95.0% C.I. for Odd | |||
---|---|---|---|---|---|---|---|
B | S.E. | t | p-Value | Lower | Upper | ||
BMI | −0.004 | 0.006 | −0.036 | −0.585 | 0.560 | −0.015 | 0.008 |
HSP72 | −0.001 | 0.000 | −0.179 | −30.711 | 0.000 | −0.001 | 0.000 |
SIRT1 | 0.022 | 0.021 | 0.085 | 10.069 | 0.287 | −0.019 | 0.063 |
SOD | −0.007 | 0.019 | −0.049 | −0.356 | 0.722 | −0.044 | 0.031 |
Catalase | −0.007 | 0.004 | −0.260 | −10.520 | 0.131 | −0.015 | 0.002 |
LDH1 | −0.001 | 0.000 | −0.071 | −10.965 | 0.051 | −0.001 | 0.000 |
ANP | 00.000 | 0.001 | −0.003 | −0.035 | 0.972 | −0.001 | 0.001 |
HEPCIDINE | 0.001 | 0.001 | 0.124 | 10.179 | 0.240 | −0.001 | 0.003 |
FOXO1 | −0.002 | 0.001 | −0.180 | −20.131 | 0.035 | −0.003 | 0.000 |
FOXO1 gene expression | 0.038 | 0.010 | 0.625 | 30.956 | 0.000 | 0.019 | 0.057 |
Constant | 0.389 | 0.278 | 10.402 | 0.163 | −0.160 | 0.939 |
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Ibrahim, H.A.; Zakaria, S.S.; El-Batch, M.M.; El-Shanshory, M.R.; Alrayes, Z.R.; Kabel, A.M.; Eldardiry, S.A. The Value of SIRT1/FOXO1 Signaling Pathway in Early Detection of Cardiovascular Risk in Children with β-Thalassemia Major. Biomedicines 2022, 10, 2601. https://doi.org/10.3390/biomedicines10102601
Ibrahim HA, Zakaria SS, El-Batch MM, El-Shanshory MR, Alrayes ZR, Kabel AM, Eldardiry SA. The Value of SIRT1/FOXO1 Signaling Pathway in Early Detection of Cardiovascular Risk in Children with β-Thalassemia Major. Biomedicines. 2022; 10(10):2601. https://doi.org/10.3390/biomedicines10102601
Chicago/Turabian StyleIbrahim, Hoda A., Soha S. Zakaria, Manal M. El-Batch, Mohamed R. El-Shanshory, Zahrah R. Alrayes, Ahmed M. Kabel, and Samia A. Eldardiry. 2022. "The Value of SIRT1/FOXO1 Signaling Pathway in Early Detection of Cardiovascular Risk in Children with β-Thalassemia Major" Biomedicines 10, no. 10: 2601. https://doi.org/10.3390/biomedicines10102601
APA StyleIbrahim, H. A., Zakaria, S. S., El-Batch, M. M., El-Shanshory, M. R., Alrayes, Z. R., Kabel, A. M., & Eldardiry, S. A. (2022). The Value of SIRT1/FOXO1 Signaling Pathway in Early Detection of Cardiovascular Risk in Children with β-Thalassemia Major. Biomedicines, 10(10), 2601. https://doi.org/10.3390/biomedicines10102601