Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients
Abstract
1. Introduction
2. Results
2.1. Screening Stage
2.2. Quantification of Selected miRNA in Plasma Samples
2.3. Quantification of Selected miRNA in Tissue Samples
2.4. Identification of miRNA Targets
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Sample Collection
4.3. RNA Isolation and cDNA Synthesis from Plasma and Tissue Samples
4.4. miRNA Quantification
4.5. Identification of miRNA Targets
4.6. Western Blot Analysis of Target Proteins
4.7. Data Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AAA | Abdominal aortic aneurysm |
AUC | Area under curve |
ASA | Acetyl salicylic acid |
BP | Biological processes |
CE | Carotid endarterectomy |
CC | Cellular components |
COL11A1A | Collagen XI α1 |
CT | Cycle threshold |
CTL | Control |
DM | Diabetes mellitus |
DL | Dyslipidemia |
ECM | Extracellular matrix |
GO | Gene Ontology |
GSEA | Gene set enrichment analysis |
HTN | Hypertension |
ITGAV | Integrin α5 |
LAMB3 | Laminin 3β subunit |
LASP1 | LIM and SH3 domain protein 1 |
miRNA | microRNA |
MF | Molecular function |
MMP | Matrix Metalloproteinases |
THBS2 | Thrombospondin 2 |
VSMC | Vascular smooth muscle cells |
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Variable | CTL | AAA | CE |
---|---|---|---|
Participants Included in the Screening Stage of the Plasma Study | |||
n = 7 | n = 7 | - | |
Sex (male) | 7 (100.0%) | 7 (100.0%) | - |
Age (SD) | 62 (3) | 72 (7) | - |
HTN | 5 (71.4%) | 7 (100.0%) | - |
DM | 2 (28.6%) | 2 (28.6%) | - |
DL | 5 (71.4%) | 6 (85.7%) | - |
Smoking * | 4 (57.1%) | 2 (28.6%) | - |
Participants included in the complete plasma study | |||
n = 16 | n = 30 | n = 11 | |
Sex (male) | 16 (100.0%) | 30 (100.0%) | 11 (100.0%) |
Age (SD) | 63 (5) | 74 (8) | 68 (6) |
HTN | 10 (62.5%) | 27 (90.0%) | 7 (63.6%) |
DM | 2 (12.5%) | 13 (43.3%) | 6 (54.5%) |
DL | 14 (87.5%) | 20 (66.7%) | 7 (63.6%) |
Smoking * | 4 (25.0%) | 14 (46.7%) | 8 (72.7%) |
Open Surgery | - | 10 (33.3%) | - |
Aneurysm Diameter, mm (SD) | - | 57.3 (10.3) | - |
Statin use | 4 (25.0%) | 21 (70.0%) | 10 (90.9%) |
Anti-hypertensives (no beta-blockers) | 10 (62.5%) | 23 (76.7%) | 7 (63.6%) |
Anti-hypertensives (beta-blockers) | 2 (12.5%) | 8 (26.7%) | 4 (36.4%) |
ASA | 2 (12.5%) | 11 (36.7%) | 7 (63.6%) |
Other antiplatelet therapies | 1 (6.3%) | 5 (16.7%) | 3 (27.3%) |
Anti-coagulants | 0 (0.0%) | 4 (13.3%) | 1 (9.1%) |
Participants included in the complete tissue study | |||
n = 8 | n = 21 | - | |
Sex (male) | - | 20 (95.2%) | - |
Age (SD) | - | 65.3 (6.5) | - |
HTN | - | 17 (81.0%) | - |
DM | - | 10 (47.6%) | - |
DL | - | 13 (61.9%) | - |
Smoking * | - | 10 (47.6%) | - |
Open Surgery | - | 21 (100.0%) | - |
Aneurysm Diameter, mm (SD) | - | 61.7 (10.9) | - |
Statin use | - | 14 (66.7%) | - |
Anti-hypertensives (no beta-blockers) | - | 16 (76.2%) | - |
Anti-hypertensives (beta-blockers) | - | 6 (28.6%) | - |
ASA | - | 4 (19.0%) | - |
Other antiplatelet therapies | - | 3 (14.3%) | - |
Anti-coagulants | - | 3 (14.3%) | - |
miRNA Name | Fold-Change (AAA/CTL) |
---|---|
miR-27b-3p | 1.39 |
miR-339-3p | 1.92 |
let-7g-5p | 1.10 |
miR-152-3p | 2.52 |
miR-7-1-3p | −2.27 |
miR-375 | 2.45 |
miR-103a-3p | −1.39 |
miR-193a-5p | 3.44 |
miR-154-5p | 1.01 |
miR-326 | 2.59 |
miR-362-3p | −1.37 |
miR-140-3p | 1.45 |
miR-144-3p | −2.27 |
miR-146a-5p | 1.66 |
miR-130b-3p | 1.51 |
miR-1260a | 2.06 |
miR-29a-3p | 1.34 |
miR-144-5p | 1.23 |
miR-100-5p | 1.65 |
miR-106b-5p | −1.27 |
miR-766-3p | 1.73 |
miR-125a-5p | 1.42 |
miR-142-5p | 1.23 |
miR-22-3p | 1.96 |
miR-221-3p | 1.50 |
miR-99a-5p | 2.71 |
miR-30e-3p | 1.81 |
let-7b-3p | 3.24 |
miR-125b-5p | 1.34 |
miRNA Name | miRNA Sequence | Fold-Change (AAA vs. CTL) | p-Value | Estimate | Lower 95% | Upper 95% |
---|---|---|---|---|---|---|
miR-152-3p | ucagugcaugacagaacuugg | 1.5 | 0.357 | 0.028 | −0.032 | 0.087 |
miR-144-3p | uacaguauagaugauguacu | 1 | 0.804 | −0.230 | −2.081 | 1.621 |
miR-27b-3p | uucacaguggcuaaguucugc | 1.6 | 0.043 | 0.427 | 0.014 | 0.841 |
miR-103a-3p | agcagcauuguacagggcuauga | 1 | 0.284 | 0.528 | −0.452 | 1.509 |
miR-99a-5p | aacccguagauccgaucuugug | 1.9 | 0.183 | 0.081 | −0.04 | 0.201 |
miR-375 | uuuguucguucggcucgcguga | 2 | 0.139 | 0.075 | −0.025 | 0.174 |
miR-221-3p | agcuacauugucugcuggguuuc | 1.9 | 0.001 | 0.333 | 0.145 | 0.521 |
miR-146a-5p | ugagaacugaauuccauggguu | 1.6 | 0.457 | 0.054 | −0.09 | 0.198 |
miR-1260 | aucccaccucugccacca | 2 | 0.238 | 0.049 | −0.034 | 0.132 |
miRNA Name | miRNA Sequence | Fold-Change (AAA vs. CTL) | p-Value | Estimate | Lower 95% | Upper 95% |
---|---|---|---|---|---|---|
miR-221-3p | agcuacauugucugcuggguuuc | 1.1 | 0.742 | 0.171 | −0.885 | 1.226 |
miR-27b-3p | uucacaguggcuaaguucugc | −2.0 | <0.001 | −15.244 | −22.319 | −8.169 |
miR-99a-5p | aacccguagauccgaucuugug | 1.4 | 0.277 | 1.947 | −1.653 | 5.548 |
miR-103a-3p | agcagcauuguacagggcuauga | 1.3 | 0.050 | 3.856 | 0.007 | 7.705 |
miR-146a-5p | ugagaacugaauuccauggguu | 5.8 | <0.001 | 1.251 | 0.662 | 1.840 |
miR-1260 | aucccaccucugccacca | 1.2 | 0.677 | 0.379 | −1.464 | 2.221 |
miR-144-3p | uacaguauagaugauguacu | 7.2 | 0.001 | 19.002 | 8.656 | 29.348 |
miR-152-3p | ucagugcaugacagaacuugg | 1.1 | 0.380 | 0.246 | −0.320 | 0.813 |
miR-195-5p | uagcagcacagaaauauuggc | −1.5 | 0.023 | −2.248 | −4.163 | −0.333 |
miR-155-5p | uuaaugcuaaucgugauagggguu | 1.9 | 0.082 | 0.316 | −0.043 | 0.676 |
miR-21-5p | uagcuuaucagacugauguuga | 1.9 | 0.012 | 86.025 | 20.360 | 151.689 |
miR-133b | uuugguccccuucaaccagcua | −4.6 | <0.001 | −2.82 | −3.637 | −2.002 |
miR-133a | uuugguccccuucaaccagcug | −4.4 | <0.001 | −1.643 | −2.150 | −1.135 |
miR-1 | uggaauguaaagaaguauguau | −4.4 | <0.001 | −1.628 | −2.105 | −1.150 |
miR-29b-3p | uagcaccauuugaaaucaguguu | −1.4 | 0.018 | −3.509 | −6.373 | −0.645 |
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Plana, E.; Gálvez, L.; Medina, P.; Navarro, S.; Fornés-Ferrer, V.; Panadero, J.; Miralles, M. Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients. Int. J. Mol. Sci. 2020, 21, 4600. https://doi.org/10.3390/ijms21134600
Plana E, Gálvez L, Medina P, Navarro S, Fornés-Ferrer V, Panadero J, Miralles M. Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients. International Journal of Molecular Sciences. 2020; 21(13):4600. https://doi.org/10.3390/ijms21134600
Chicago/Turabian StylePlana, Emma, Laura Gálvez, Pilar Medina, Silvia Navarro, Victoria Fornés-Ferrer, Joaquín Panadero, and Manuel Miralles. 2020. "Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients" International Journal of Molecular Sciences 21, no. 13: 4600. https://doi.org/10.3390/ijms21134600
APA StylePlana, E., Gálvez, L., Medina, P., Navarro, S., Fornés-Ferrer, V., Panadero, J., & Miralles, M. (2020). Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients. International Journal of Molecular Sciences, 21(13), 4600. https://doi.org/10.3390/ijms21134600