MiRNA-21a, miRNA-145, and miRNA-221 Expression and Their Correlations with WNT Proteins in Patients with Obstructive and Non-Obstructive Coronary Artery Disease
Abstract
:1. Introduction
2. Results
2.1. Basic Clinical Characteristics
2.2. Concentration of WNT Proteins in Plasma
2.3. MiRNA Expression in Plasma of Patients with CAD
2.4. Correlations of WNT Proteins with Circulating miRNAs
3. Discussion
4. Materials and Methods
4.1. Patient Population
4.2. Collection of Blood Samples and ELISA
4.3. RNA Extraction and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Assay
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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All CAD (n = 64) | INOCA (n = 20) | Obstructive CAD (n = 44) | Control (n = 30) | p-Value | |
---|---|---|---|---|---|
Men (%) | 33 (51.6) | 5 (25) | 28 (63.6) | 10 (33.3) | 0.004 * p INOCA–obstructive CAD = 0.012 p obstructive CAD–Control = 0.021 |
Women (%) | 31 (48.4) | 15 (75) | 16 (36.4) | 20 (66.7) | |
Age (year) | 65 [59; 71] | 66.5 [62.8; 71.2] | 64.0 [56.5; 71] | 28.5 [26; 39.2] | <0.001 * p control–INOCA < 0.001 p control–obstructive CAD < 0.001 |
BMI (kg/m2) | 26.7 [24.9; 28.8] | 26.20 [25.67; 30.40] | 26.23 [24.68; 28.68] | 21.95 [20.75; 25.23] | <0.001 * p control–INOCA = 0.003 p control–obstructive CAD = 0.003 |
Smoking (%) | 9 (14) | 3 (15.0) | 6 (13.6) | - | 0.879 |
Hemoglobin (g/L) | 142 [133; 152] | 142 [134; 151] | 144 [133; 152] | 136 [129; 152] | 0.459 |
Glucose (mmol/L) | 5.5 [5.17; 5.8] | 5.60 [5.2; 6.21] | 5.40 [5.1; 5.63] | 4.9 [4.59; 5.35] | <0.001 |
Creatinine (µmol/L) | 89 [78.2; 99.2] | 83.4 [74.8; 96.3] | 89.80 [81; 101.8] | 82 [77.7; 87] | 0.106 |
Total cholesterol (mmol/L) | 4.39 ± 1.36 | 5.11 ± 1.51 | 3.85 ± 0.95 | 4.87 ± 0.77 | <0.001 * p INOCA– obstructive CAD = 0.005 p obstructive CAD–Control < 0.001 |
LDL (mmol/L) | 2.36 [1.85; 2.97] | 2.89 [4.34; 3.62] | 2.12 [1.79; 2.48] | 2.54 [2.28; 3.21] | <0.001 * p obstructive CAD–INOCA < 0.001 p control–obstructive CAD = 0.049 |
HDL (mmol/L) | 1.15 [1.02; 1.36] | 1.27 [1.06; 1.37] | 1.11 [1.02; 1.33] | 1.62 [1.35; 1.9] | <0.001 * p control–INOCA = 0.015 p control–obstructive CAD < 0.001 |
INOCA | Obstructive CAD | p-Value | |
---|---|---|---|
ACE inhibitors | 9 (45.0) | 27 (62.8) | 0.184 |
ARB II | 6 (30.0) | 10 (23.3) | 0.567 |
Beta-blocker | 17 (85.0) | 34 (79.1) | 0.737 |
Calcium channel blockers | 11 (55.0) | 18 (41.9) | 0.33 |
Antiaggregants | 16 (80.0) | 40 (93.0) | 0.195 |
Antiarrhythmic drugs | 3 (10.3) | 6 (20.0) | 0.237 |
HMG-CoA reductase inhibitors | 19 (95.0) | 44 (100.0) | 0.323 |
Anticoagulants | 4 (15) | 6 (13.6) | 1.000 |
Proteins | Groups | Concentration (Me [Q1–Q3]) | p-Value |
---|---|---|---|
LRP6, ng/mL | INOCA | 13.02 [12.05–13.7] | 0.075 |
Obstructive CAD | 11.60 [10.5–12.88] | ||
Control | 12.55 [10.28–14.17] | ||
WNT1, ng/mL | INOCA | 0.15 [0.15–0.16] | <0.001 * p obstructive CAD–INOCA < 0.001 p control–INOCA = 0.036 p control–CAD < 0.001 |
Obstructive CAD | 0.189 [0.184–0.193] | ||
Control | 0.15 [0.15–0.184] | ||
WNT3a, ng/mL | INOCA | 0.115 [0.07–0.16] | <0.001 * p obstructive CAD–INOCA < 0.001 p control–INOCA < 0.001 |
Obstructive CAD | 0.227 [0.181–0.252] | ||
Control | 0.25 [0.162–0.37] | ||
WNT4, ng/mL | INOCA | 0.345 [0.278–0.492] | 0.015 * p obstructive CAD–INOCA = 0.025 p control–obstructive CAD = 0.047 |
Obstructive CAD | 0.203 [0.112–0.378] | ||
Control | 0.345 [0.232–0.528] | ||
WNT5a, ng/mL | INOCA | 0.17 [0.16–0.17] | <0.001 * p obstructive CAD–INOCA < 0.001 p control–obstructive CAD = 0.001 |
Obstructive CAD | 0.01 [0.007–0.018] | ||
Control | 0.16 [0.015–0.17] | ||
SIRT1, ng/mL | INOCA | 1.09 [1.09–1.1] | <0.001 * p obstructive CAD–INOCA < 0.001 p control–INOCA = 0.012 p control–obstructive CAD = 0.007 |
Obstructive CAD | 0.079 [0.066–0.104] | ||
Control | 1.09 [0.035–1.1] |
Factor/Predictor | B | OR (95%CI) Exp (B) [95%CI] | p-Value |
---|---|---|---|
miR-21a (REU) | −2.568 | 0.077 [0.001. 5.757] | p = 0.244 |
miR-145 (REU) | −2.02 | 0.133 [0.0. 62.492] | p = 0.520 |
miR-221 (REU) | −1.122 | 0.326 [0.0. 283.87] | p = 0.745 |
LRP6 (ng/mL) | 0.475 | 1.608 [1.037. 2.494] | p = 0.034 * |
WNT1 (ng/mL) | −1808.16 | 0.0 [0.0. inf] | p = 0.999 |
WNT3A (ng/mL) | −30.917 | 0.0 [0.0. 0.00005] | p = 0.001 * |
WNT4 (ng/mL) | −0.321 | 0.725 [0.368. 1.429] | p = 0.354 |
WNT5a (ng/mL) | 2.466 | 11.775 [0.298. 465.105] | p = 0.188 |
SIRT1 (ng/mL) | 64.169 | 7.38e + 27 [0.0. inf] | p = 0.994 |
Age (years) | 0.036 | 1.037 [0.969. 1.11] | p = 0.297 |
Smoking (n) | 0.111 | 1.117 [0.25. 5.005] | p = 0.884 |
Gender (male/female) | −1.658 | 0.191 [0.058. 0.622] | p = 0.006 * |
BMI (kg/m2) | 0.041 | 1.042 [0.891. 1.218] | p = 0.605 |
Hypertension (n) | 0.329 | 1.39 [0.136. 14.255] | p = 0.781 |
Dyslipidemia (n) | 0.329 | 1.39 [0.136. 14.255] | p = 0.781 |
Angina pain (n) | 0.542 | 1.719 [0.417. 7.084] | p = 0.454 |
Myocardial infarction (n) | −1.923 | 0.146 [0.03. 0.708] | p = 0.017 * |
ACE inhibitors | −0.724 | 0.485 [0.165. 1.422] | p = 0.187 |
ARB II | 0.347 | 1.415 [0.43. 4.647] | p = 0.568 |
Beta blockers | 0.405 | 1.499 [0.359. 6.271] | p = 0.579 |
Calcium channel blockers | 0.529 | 1.697 [0.583. 4.945] | p = 0.332 |
Antiaggregant | −1.204 | 0.3 [0.06. 1.494] | p = 0.142 |
Statins | −21.683 | 0.0 [0.0. inf] | p = 0.999 |
Fasting glucose (mmol/l) | −0.021 | 0.979 [0.898. 1.067] | p = 0.635 |
Variables | Coef (B) | Exp (B) | p-Value |
---|---|---|---|
LRP6, ng/mL | 0.451 | 1.57 [1.17. 2.09] | p = 0.002 * |
WNT3a, ng/mL | −34.4454 | 0.0 [0.0. 0.00001] | p < 0.001 |
Primer | Sequence |
---|---|
miR-21a | 5′-TAGCTTATCAGACTGATGTTGAAAA-3′ |
miR-145 | 5′-TCCAGTTTTCCCAGGAATCCCT-3′ |
miR-221 | 5′-GACCTGGCATACAATGTAGATTTAAA-3′ |
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Iusupova, A.O.; Pakhtusov, N.N.; Slepova, O.A.; Belenkov, Y.N.; Privalova, E.V.; Bure, I.V.; Vetchinkina, E.A.; Nemtsova, M.V. MiRNA-21a, miRNA-145, and miRNA-221 Expression and Their Correlations with WNT Proteins in Patients with Obstructive and Non-Obstructive Coronary Artery Disease. Int. J. Mol. Sci. 2023, 24, 17613. https://doi.org/10.3390/ijms242417613
Iusupova AO, Pakhtusov NN, Slepova OA, Belenkov YN, Privalova EV, Bure IV, Vetchinkina EA, Nemtsova MV. MiRNA-21a, miRNA-145, and miRNA-221 Expression and Their Correlations with WNT Proteins in Patients with Obstructive and Non-Obstructive Coronary Artery Disease. International Journal of Molecular Sciences. 2023; 24(24):17613. https://doi.org/10.3390/ijms242417613
Chicago/Turabian StyleIusupova, Alfiya Oskarovna, Nikolay Nikolaevich Pakhtusov, Olga Alexandrovna Slepova, Yuri Nikitich Belenkov, Elena Vitalievna Privalova, Irina Vladimirovna Bure, Ekaterina Alexandrovna Vetchinkina, and Marina Vyacheslavovna Nemtsova. 2023. "MiRNA-21a, miRNA-145, and miRNA-221 Expression and Their Correlations with WNT Proteins in Patients with Obstructive and Non-Obstructive Coronary Artery Disease" International Journal of Molecular Sciences 24, no. 24: 17613. https://doi.org/10.3390/ijms242417613