Circular RNA Profile in Atherosclerotic Disease: Regulation during ST-Elevated Myocardial Infarction
Abstract
:1. Introduction
2. Results
2.1. Atherogenesis Alters the circRNA Expression: Pre-Clinical Explorative Studies
2.2. Atherogenic circRNA Translated to Human Homologs
2.3. circRNA Expression in Patients with STEMI
2.4. Negative Correlation between circRNA Levels and Peak TnT Levels and Final Infarct Size
2.5. Regulation of mRNA Targets for the circRNA–miRNA Interaction
2.6. circRNA Expression with IL-6R Inhibition
3. Discussion
4. Materials and Methods
4.1. Ethics
4.2. Mouse Models
4.3. Murine Circular RNA Array
4.4. Primer Design
4.5. Human Total RNA-Isolation and cDNA Synthesis
4.6. Quantitative Reverse Transcriptase PCR
4.7. miRNA and mRNA Targets
4.8. RNA Sequencing
4.9. Patients and Study Design of ASSAIL-MI
4.10. Blood Sampling Protocol
4.11. Measurement of Cardiac Markers in the ASSAIL-MI Trial
4.12. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
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Placebo (n = 19) A | Tocilizumab (n = 21) B | |
---|---|---|
Demographics | ||
Age, years | 64 ± 6 | 65 ± 6 |
Body mass index, kg/m2 | 24.4 ± 2.8 | 25.2 ± 3.3 |
Male | 9 (47) | 11 (52) |
White | 19 (100) | 21 (100) |
Smoking status | ||
Never smokers | 6 (32) | 7 (33) |
Previous smokers | 4 (21) | 7 (33) |
Current smokers | 9 (47) | 7 (33) |
Prior conditions | ||
Angina pectoris | 1 (5) | 0 |
Cerebrovascular disease | 1 (5) | 1 (5) |
Hypertension | 7 (37) | 7 (33) |
Treatment | ||
ACE inhibitor or ARB | 4 (21) | 1 (5) |
Oral anticoagulants | 0 | 1 (5) |
Platelet inhibitor | 1 (5) | 3 (14) |
Beta-blocker | 1 (5) | 4 (19) |
Calcium antagonist | 2 (10) | 3 (14) |
Diuretic | 1 (5) | 0 |
Statin | 3 (16) | 5 (24) |
Up-front DAPT | 19 (100) | 21 (100) |
Clinical characteristics | ||
Blood pressure at admission, mm Hg | ||
Systolic | 124 ± 22 | 130 ± 23 |
Diastolic | 77 ± 14 | 77 ± 21 |
Heart rate at admission, beats/min | 70 ± 16 | 70 ± 15 |
Time from symptom onset to arrival at PCI center, min | 184 ± 80 | 144 ± 64 |
Door-to-balloon time, min | 27 ± 15 | 21 ± 8 |
Killip class | ||
I | 18 (95) | 20 (95) |
II | 1 (5) | 1 (5) |
GRACE risk score | 147 ± 20 | 147 ± 24 |
Infarct location | ||
Left anterior descending branch | 3 (16) | 5 (24) |
Circumflex or marginal | 5 (26) | 2 (10) |
Right coronary artery | 11 (58) | 13 (62) |
Laboratory values | ||
Hemoglobin, g/dL | 14.1 ± 1.3 | 13.9 ± 1.5 |
Platelet count, 109/L | 251 ± 52 | 261 ± 64 |
Total white blood cell count, 109/L | 10.5 ± 3.4 | 11.7 ± 4.0 |
Aspartate transaminase, U/L | 29 (24–39) | 29 (23–38) |
Troponin T, ng/L | 58 (28–95) | 33 (19–62) |
CK-MB, μg/L | 6.0 (2.8–23.8) | 4.4 (2.7–6.3) |
NT-proBNP, ng/L | 155 (58–347) | 107 (52–212) |
Creatinine, mmol/L | 64 ± 13 | 70 ± 13 |
Glucose, mmol/L | 8.1 ± 2.0 | 8.2 ± 1.3 |
HbA1c, mmol/mol | 36 (33–48) | 38 (36–39) |
Total cholesterol, mmol/L | 5.5 ± 1.1 | 5.4 ± 1.1 |
HDL cholesterol, mmol/L | 1.3 (1.1–1.7) | 1.2 (1.0–1.3) |
LDL cholesterol, mmol/L | 3.8 ± 0.9 | 3.9 ± 1.0 |
C-reactive protein, mg/L | 4.1 (2.1–5.0) | 1.7 (0.9–5.0) |
Albumin, g/L | 42 ± 6 | 40 ± 3 |
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Holme, F.A.; Huse, C.; Kong, X.Y.; Broch, K.; Gullestad, L.; Anstensrud, A.K.; Andersen, G.Ø.; Amundsen, B.H.; Kleveland, O.; Quiles-Jimenez, A.; et al. Circular RNA Profile in Atherosclerotic Disease: Regulation during ST-Elevated Myocardial Infarction. Int. J. Mol. Sci. 2024, 25, 9014. https://doi.org/10.3390/ijms25169014
Holme FA, Huse C, Kong XY, Broch K, Gullestad L, Anstensrud AK, Andersen GØ, Amundsen BH, Kleveland O, Quiles-Jimenez A, et al. Circular RNA Profile in Atherosclerotic Disease: Regulation during ST-Elevated Myocardial Infarction. International Journal of Molecular Sciences. 2024; 25(16):9014. https://doi.org/10.3390/ijms25169014
Chicago/Turabian StyleHolme, Fredric A., Camilla Huse, Xiang Yi Kong, Kaspar Broch, Lars Gullestad, Anne Kristine Anstensrud, Geir Ø. Andersen, Brage H. Amundsen, Ola Kleveland, Ana Quiles-Jimenez, and et al. 2024. "Circular RNA Profile in Atherosclerotic Disease: Regulation during ST-Elevated Myocardial Infarction" International Journal of Molecular Sciences 25, no. 16: 9014. https://doi.org/10.3390/ijms25169014