HIGHLIGHTS
- •MiRNAs are good candidates as circulating biomarkers (stability in human blood and high sensitivity/ specificity of expression evaluation).
- •Numerous reports have recently demonstrated differential expression of miRNAs in Cardiovascular, Peripheral Arterial and Aneurysmal disease.
- •A total of 25 reports, published from 2012 to 2022, were included in this review (N=1259 patients with AAA, 90% men).
- •The following miRNAs were identified in more than two references: miR-145, miR-24, miR-33, miR-125, let-7, miR-15, miR-191, miR-29 and miR-133.
- •These nine miRNAs are implicated in known pathogenetic mechanisms for AAA.
Abstract
OBJECTIVE
To provide a summary of the current state of research in English medical literature
on circulating miRNAs, as biomarkers for AAA. Additionally, for the most commonly
mentioned circulating miRNAs in the literature, to attempt a documentation of the
biological mechanisms underlying their role in AAA development.
METHODS
A literature search was undertaken in the MEDLINE database. Only reports that involved
peripheral blood samples (whole blood, plasma, serum) were included. The following
terms were used in combination: microrna, mirna, abdominal aortic aneurysm, human,
circulating, plasma, serum, endovascular and EVAR.
RESULTS
A total of 25 reports, published from 2012 to 2022 were included with a total of 1259
patients with AAA, predominantly men (N= 1040, 90%). Six of these reports recruited
healthy donors who underwent ultrasound screening for AAA as control samples. The
majority of studies were undertaken in plasma samples and the most preferred microRNA
profiling method was Real - Time quantitative polymerase chain reaction (qRT-PCR).
The following nine miRNAs (out of a total of 76) were studied in more than two references:
miR-145, miR-24, miR-33, miR-125, let-7, miR-15, miR-191, miR-29 and miR-133.
CONCLUSION
The nine miRNAs described in this study, are implicated in known pathogenetic mechanisms
of AAA such as atherosclerosis, vascular smooth muscle cell phenotype switch and apoptosis,
vascular inflammation, extracellular matrix degradation and lipid metabolism. Identifying
disease-specific miRNAs, in combination with other clinical parameters, as indicators
of AAA, is crucial for early diagnosis as well as follow-up of AAAs. For future research
on miRNAs as AAA biomarkers, strict case and control group definitions, sample acquisition
protocols, and miRNA expression profiling techniques are warranted.
Keywords
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9. References
- Screening Program of Abdominal Aortic Aneurysm.Angiology. 2019; 70: 407-413https://doi.org/10.1177/0003319718824940
- Age-specific incidence, risk factors and outcome of acute abdominal aortic aneurysms in a defined population.Br J Surg. 2015; 102: 907-915https://doi.org/10.1002/bjs.9838
- Role of Noncoding RNAs in the Pathogenesis of Abdominal Aortic Aneurysm: Possible Therapeutic Targets?.Circ Res. 2019; 124: 619-630https://doi.org/10.1161/CIRCRESAHA.118.312438
- Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm.Int J Mol Sci. 2020; 21: 6334https://doi.org/10.3390/ijms21176334
- Clinical Application of Serum microRNAs in Atherosclerotic Coronary Artery Disease.J Clin Med. 2022; 11: 6849https://doi.org/10.3390/jcm11226849
- Analytical challenges and technical limitations in assessing circulating MiRNAs.Thromb Haemost. 2012; 108: 592-598https://doi.org/10.1160/TH12-02-0097
- Association of miRNA-145 Single Nucleotide Polymorphisms in Abdominal Aortic Aneurysms.In Vivo. 2022; 36: 1120-1125https://doi.org/10.21873/invivo.12810
- Circulating microRNA in patients with popliteal and multiple artery aneurysms.JVS Vasc Sci. 2021; 2: 129-135https://doi.org/10.1016/j.jvssci.2021.04.003
- Circulating microRNAs signature correlates with positive [18F]fluorodeoxyglucose-positron emission tomography in patients with abdominal aortic aneurysm.J Vasc Surg. 2018; 67: 585-595.e3https://doi.org/10.1016/j.jvs.2016.12.112
- Detection of Atherosclerosis by Small RNA-Sequencing Analysis of Extracellular Vesicle Enriched Serum Samples.Front Cell Dev Biol. 2021; 9729061https://doi.org/10.3389/fcell.2021.729061
- Differential micro-RNA expression in diabetic patients with abdominal aortic aneurysm.Biochimie. 2019; 162: 1-7https://doi.org/10.1016/j.biochi.2019.03.012
- Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm.J Clin Med. 2020; 9: 1974https://doi.org/10.3390/jcm9061974
- Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm.Int J Mol Sci. 2015; 16: 11276-11293https://doi.org/10.3390/ijms160511276
- Expression in Whole Blood Samples of miRNA-191 and miRNA-455-3p in Patients with AAA and Their Relationship to Clinical Outcomes after Endovascular Repair.Ann Vasc Surg. 2018; 50: 209-217https://doi.org/10.1016/j.avsg.2018.01.086
- Expression of MicroRNA-1281, C-Reactive Protein, and Renal Function in Individuals with Abdominal Aortic Aneurysm and their Clinical Correlation after Endovascular Repair.Braz J Cardiovasc Surg. 2021; 36 (Epub ahead of print)https://doi.org/10.21470/1678-9741-2020-0268
- Identification of a Plasma Microrna Signature as Biomarker of Subaneurysmal Aortic Dilation in Patients with High Cardiovascular Risk.J Clin Med. 2020; 9: 2783https://doi.org/10.3390/jcm9092783
- Identification of microRNAs associated with abdominal aortic aneurysms and peripheral arterial disease.Br J Surg. 2015; 102: 755-766https://doi.org/10.1002/bjs.9802
- Let-7f: A New Potential Circulating Biomarker Identified by miRNA Profiling of Cells Isolated from Human Abdominal Aortic Aneurysm.Int J Mol Sci. 2019; 20: 5499https://doi.org/10.3390/ijms20215499
- microRNA profiling in patients with abdominal aortic aneurysms: the significance of miR-155.Clin Sci. 2014; 126: 795-803https://doi.org/10.1042/CS20130599
- MicroRNA-26a protects vascular smooth muscle cells against H2O2-induced injury through activation of the PTEN/AKT/mTOR pathway.Int J Mol Med. 27 June 2018; (Epub ahead of print)https://doi.org/10.3892/ijmm.2018.3746
- miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development.Nat Commun. 2014; 5: 5214https://doi.org/10.1038/ncomms6214
- miR-124a Involves in the Regulation of Wnt/β-Catenin and P53 Pathways to Inhibit Abdominal Aortic Aneurysm via Targeting BRD4.Comput Math Methods Med 2022. 2022; : 1-11https://doi.org/10.1155/2022/9241959
- miR-146a regulates inflammation and development in patients with abdominal aortic aneurysms by targeting CARD10.Int Angiol. October 2020; 39 (Epub ahead of print)https://doi.org/10.23736/S0392-9590.20.04283-2
- MiR-191 as a Key Molecule in Aneurysmal Aortic Remodeling.Biomolecules. 2021; 11: 1611https://doi.org/10.3390/biom11111611
- miR-195 suppresses abdominal aortic aneurysm through the TNF-α/NF-κB and VEGF/PI3K/Akt pathway.Int J Mol Med. 25 January 2018; (Epub ahead of print)https://doi.org/10.3892/ijmm.2018.3426
- Nuclear Paraspeckle Assembly Transcript 1 Enhances Hydrogen Peroxide-Induced Human Vascular Smooth Muscle Cell Injury by Regulating miR-30d-5p/A Disintegrin and Metalloprotease 10.Circ J. 2022; 86: 1007-1018https://doi.org/10.1253/circj.CJ-21-0042
- Plasma microRNAs serve as potential biomarkers for abdominal aortic aneurysm.Clin Biochem. 2015; 48: 988-992https://doi.org/10.1016/j.clinbiochem.2015.04.016
- Role of miR-195 in Aortic Aneurysmal Disease.Circ Res. 2014; 115: 857-866https://doi.org/10.1161/CIRCRESAHA.115.304361
- Screening of circulating microRNA biomarkers for prevalence of abdominal aortic aneurysm and aneurysm growth.Atherosclerosis. 2017; 256: 82-88https://doi.org/10.1016/j.atherosclerosis.2016.11.007
- Tissue‐ and Plasma‐Specific MicroRNA Signatures for Atherosclerotic Abdominal Aortic Aneurysm.J Am Heart Assoc. 2012; 1e000745https://doi.org/10.1161/JAHA.112.000745
- Up-regulation of exosomal miR-106a may play a significant role in abdominal aortic aneurysm by inducing vascular smooth muscle cell apoptosis and targeting TIMP-2, an inhibitor of metallopeptidases that suppresses extracellular matrix degradation.Eur Rev Med Pharmacol Sci. 2020; 24: 8087-8095https://doi.org/10.26355/eurrev_202008_22493
- Mechanisms of aortic aneurysm formation: translating preclinical studies into clinical therapies.Heart. 2014; 100: 1498-1505https://doi.org/10.1136/heartjnl-2014-305648
- MicroRNA-145, a Novel Smooth Muscle Cell Phenotypic Marker and Modulator, Controls Vascular Neointimal Lesion Formation.Circ Res. 2009; 105: 158-166https://doi.org/10.1161/CIRCRESAHA.109.197517
Mirbase https://www.mirbase.org/ (accessed December 14, 2022).
- The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease.Cell Death Differ. 2009; 16: 1590-1598https://doi.org/10.1038/cdd.2009.153
- A microRNA profile comparison between thoracic aortic dissection and normal thoracic aorta indicates the potential role of microRNAs in contributing to thoracic aortic dissection pathogenesis.J Vasc Surg. 2011; 53: 1341-1349.e3https://doi.org/10.1016/j.jvs.2010.11.113
- Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster.J Clin Invest. 2009; 119: 2634-2647https://doi.org/10.1172/JCI38864
- MicroRNA Regulation of Vascular Smooth Muscle Function and Phenotype: Early Career Committee Contribution.Arterioscler Thromb Vasc Biol. 2015; 35: 2-6https://doi.org/10.1161/ATVBAHA.114.304877
- TGF-β signaling and microRNA cross-talk regulates abdominal aortic aneurysm progression.Clin Chim Acta. 2021; 515: 90-95https://doi.org/10.1016/j.cca.2020.12.031
- Dysregulation of microRNAs and target genes networks in human abdominal aortic aneurysm tissues.PLoS One. 2019; 14e0222782https://doi.org/10.1371/journal.pone.0222782
- MicroRNAs as possible biomarkers for screening of aortic aneurysms: a systematic review and validation study.Biomarkers. 2018; 23: 253-264https://doi.org/10.1371/journal.pone.0222782
- miRNAs in endothelial cell signaling: The endomiRNAs.Exp Cell Res. 2013; 319: 1324-1330https://doi.org/10.1016/j.yexcr.2012.12.009
- MicroRNA-24 Regulates Vascularity After Myocardial Infarction.Circulation. 2011; 124: 720-730https://doi.org/10.1161/CIRCULATIONAHA.111.039008
- Uncovering potential differentially expressed miRNAs and targeted mRNAs in myocardial infarction based on integrating analysis.Mol Med Rep. 17 September 2020; (Epub ahead of print)https://doi.org/10.3892/mmr.2020.11517
- Genetic and epigenetic regulation of abdominal aortic aneurysms.Clin Genet. 2020; 97: 815-826https://doi.org/10.1111/cge.13705
- MicroRNA-33: natureʼs own RNAi controls cholesterol homeostasis.Curr Opin Lipidol. 2010; 21: 464-465https://doi.org/10.1097/MOL.0b013e32833e4eea
- MicroRNA-33-5p inhibits cholesterol efflux in vascular endothelial cells by regulating citrate synthase and ATP-binding cassette transporter A1.BMC Cardiovasc Disord. 2021; 21: 433https://doi.org/10.1186/s12872-021-02228-7
- Statin-Induced Decrease in ATP-Binding Cassette Transporter A1 Expression via microRNA33 Induction may Counteract Cholesterol Efflux to High-Density Lipoprotein.Cardiovasc Drugs Ther. 2015; 29: 7-14https://doi.org/10.1007/s10557-015-6570-0
- MicroRNA-33–dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis.J Clin Invest. 2015; 125: 4334-4348https://doi.org/10.1172/JCI81676
- microRNA-33 Regulates Macrophage Autophagy in Atherosclerosis.Arterioscler Thromb Vasc Biol. 2017; 37: 1058-1067https://doi.org/10.1161/ATVBAHA.116.308916
- MicroRNA-33 protects against neointimal hyperplasia induced by arterial mechanical stretch in the grafted vein.Cardiovasc Res. 2017; 113: 488-497https://doi.org/10.1093/cvr/cvw257
- Genetic Ablation of MicroRNA-33 Attenuates Inflammation and Abdominal Aortic Aneurysm Formation via Several Anti-Inflammatory Pathways.Arterioscler Thromb Vasc Biol. 2017; 37: 2161-2170https://doi.org/10.1161/ATVBAHA.117.309768
- MicroRNA-125b Affects Vascular Smooth Muscle Cell Function by Targeting Serum Response Factor.Cell Physiol Biochem. 2018; 46: 1566-1580https://doi.org/10.1159/000489203
- MiR-125 Family in Cardiovascular and Cerebrovascular Diseases.Front Cell Dev Biol. 2021; 9799049https://doi.org/10.3389/fcell.2021.799049
- MicroRNA-125b inhibits the proliferation of vascular smooth muscle cells induced by platelet-derived growth factor BB.Exp Ther Med. 2021; 22: 791https://doi.org/10.3892/etm.2021.10223
- Involvement of Myeloid Cells and Noncoding RNA in Abdominal Aortic Aneurysm Disease.Antioxid Redox Signal. 2020; 33: 602-620https://doi.org/10.1089/ars.2020.8035
- The up-regulation of endothelin-1 and down-regulation of miRNA-125a-5p, -155, and -199a/b-3p in human atherosclerotic coronary artery.Cardiovasc Pathol. 2014; 23: 217-223https://doi.org/10.1016/j.carpath.2014.03.009
- Biogenesis and regulation of the let-7 miRNAs and their functional implications.Protein Cell. 2016; 7: 100-113https://doi.org/10.1007/s13238-015-0212-y
- Differential MicroRNA Expression Profiles in Peripheral Arterial Disease.Circ Cardiovasc Genet. 2013; 6: 490-497https://doi.org/10.1161/CIRCGENETICS.111.000053
- Let-7 in Cardiovascular Diseases, Heart Development and Cardiovascular Differentiation from Stem Cells.Int J Mol Sci. 2013; 14: 23086-23102https://doi.org/10.3390/ijms141123086
- MicroRNA Expression Signature and Antisense-Mediated Depletion Reveal an Essential Role of MicroRNA in Vascular Neointimal Lesion Formation.Circ Res. 2007; 100: 1579-1588https://doi.org/10.1161/CIRCRESAHA.106.141986
- Identification of miR-130a, miR-27b and miR-210 as serum biomarkers for atherosclerosis obliterans.Clin Chim Acta. 2011; 412: 66-70https://doi.org/10.1016/j.cca.2010.09.029
- A Comprehensive Review on Function of miR-15b-5p in Malignant and Non-Malignant Disorders.Front Oncol. 2022; 12870996https://doi.org/10.3389/fonc.2022.870996
- Post-transcriptional regulation of BRCA1 through its coding sequence by the miR-15/107 group of miRNAs.Front Genet. 24 July 2015; 6 (Epub ahead of print)https://doi.org/10.3389/fgene.2015.00242
- miR-15a and miR-16 affect the angiogenesis of multiple myeloma by targeting VEGF.Carcinogenesis. 2013; 34: 426-435https://doi.org/10.1093/carcin/bgs333
- Upregulation of MicroRNA-15a Contributes to Pathogenesis of Abdominal Aortic Aneurysm (AAA) by Modulating the Expression of Cyclin-Dependent Kinase Inhibitor 2B (CDKN2B).Med Sci Monit. 2017; 23: 881-888https://doi.org/10.12659/MSM.898233
- hsa-miR-15b-5p regulates the proliferation and apoptosis of human vascular smooth muscle cells by targeting the ACSS2/PTGS2 axis.Exp Ther Med. 2021; 22: 1208https://doi.org/10.3892/etm.2021.10642
- Roles of microRNAs in abdominal aortic aneurysm pathogenesis and the possibility of their use as biomarkers.Kardiochir Torakochirurgia Pol. 2019; 16: 124-127https://doi.org/10.5114/kitp.2019.88601
- Emerging Role of microRNA Dysregulation in Diagnosis and Prognosis of Extrahepatic Cholangiocarcinoma.Genes. 2022; 13: 1479https://doi.org/10.3390/genes13081479
- Hypoxia-Induced Upregulation of lncRNA ELFN1-AS1 Promotes Colon Cancer Growth and Metastasis Through Targeting TRIM14 via Sponging miR-191-5p.Front Pharmacol. 2022; 13806682https://doi.org/10.3389/fphar.2022.806682
- Expression of miRNA1, miRNA133, miRNA191, and miRNA24, as Good Biomarkers, in Non-Small Cell Lung Cancer Using Real-Time PCR Method.Asian Pac J Cancer Prev. 2022; 23: 1565-1570https://doi.org/10.31557/APJCP.2022.23.5.1565
- MiR-191-5p Disturbed the Angiogenesis in a Mice Model of Cerebral Infarction by Targeting Inhibition of BDNF.Neurol India. 2021; 69: 1601https://doi.org/10.4103/0028-3886.333459
- miR‐191 suppresses angiogenesis by activation of NF‐kB signaling.FASEB J. 2017; 31: 3321-3333https://doi.org/10.1096/fj.201601263R
- mir-29 regulates Mcl-1 protein expression and apoptosis.Oncogene. 2007; 26: 6133-6140https://doi.org/10.1038/sj.onc.1210436
- miR-29 miRNAs activate p53 by targeting p85α and CDC42.Nat Struct Mol Biol. 2009; 16: 23-29https://doi.org/10.1038/nsmb.1533
- Cellular Mechanisms of Aortic Aneurysm Formation.Circ Res. 2019; 124: 607-618https://doi.org/10.1161/CIRCRESAHA.118.313187
- MicroRNA-29b regulation of abdominal aortic aneurysm development.Trends Cardiovac Med. 2014; 24: 1-6https://doi.org/10.1016/j.tcm.2013.05.002
- Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development.J Clin Invest. 2012; 122: 497-506https://doi.org/10.1172/JCI61598
- MicroRNA-29 in Aortic Dilation: Implications for Aneurysm Formation.Circ Res. 2011; 109: 1115-1119https://doi.org/10.1161/CIRCRESAHA.111.255737
- microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart.Genes Dev. 2008; 22: 3242-3254https://doi.org/10.1101/gad.1738708
- Differential Expression of MicroRNAs in Different Disease States.Circ Res. 2012; 110: 638-650https://doi.org/10.1161/CIRCRESAHA.111.247437
- MicroRNA-133 controls cardiac hypertrophy.Nat Med. 2007; 13: 613-618https://doi.org/10.1038/nm1582
- MicroRNA-133 Controls Vascular Smooth Muscle Cell Phenotypic Switch In Vitro and Vascular Remodeling In Vivo.Circ Res. 2011; 109: 880-893https://doi.org/10.1161/CIRCRESAHA.111.240150
- A systematic review investigating the association of microRNAs with human abdominal aortic aneurysms.Atherosclerosis. 2017; 261: 78-89https://doi.org/10.1016/j.atherosclerosis.2017.03.010
- MicroRNA expression signature in human abdominal aortic aneurysms.BMC Med Genomics. 2012; 5: 25https://doi.org/10.1186/1755-8794-5-25
- Can microRNAs improve prediction of abdominal aortic aneurysm growth?.Atherosclerosis. 2017; 256: 131-133https://doi.org/10.1016/j.atherosclerosis.2016.12.001
- Correlation of Baseline Plasma and Inguinal Connective Tissue Metalloproteinases and Their Inhibitors With Late High-Pressure Endoleak After Endovascular Aneurysm Repair: Long-term Results.J Endovasc Ther. 2019; 26: 826-835https://doi.org/10.1177/1526602819871963
- Combined Detection of Plasma Tumor Necrosis Factor-α Converting Enzyme and Notch1 is Valuable in Screening Endoleak After Endovascular Abdominal Aortic Aneurysms Repair.Ann Vasc Surg. 2021; 76: 302-308https://doi.org/10.1016/j.avsg.2021.03.041
Article info
Publication history
Accepted:
February 23,
2023
Received in revised form:
February 21,
2023
Received:
January 16,
2023
Publication stage
In Press Journal Pre-ProofIdentification
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