Skip to main content
NCBI home page
In Vivo logoLink to In Vivo
. 2022 May 3;36(3):1120–1125. doi: 10.21873/invivo.12810

Association of miRNA-145 Single Nucleotide Polymorphisms in Abdominal Aortic Aneurysms

NATASHA HASEMAKI 1, NIKOLAOS-PANAGIOTIS ANDREOU 2, EVANGELIA LEGAKI 2, ATHANASIOS KATSARGYRIS 1,3, MARIA GAZOULI 2, CHRISTOS KLONARIS 1
PMCID: PMC9087113  PMID: 35478113

Abstract

Background/Aim: MicroRNAs (miRNAs) are non-coding RNA molecules that exert post-transcriptional gene expression regulation in response to cellular or environmental changes. Genetic variation affects their synthesis and cellular actions, and single nucleotide polymorphisms (SNPs) are one example of genetic variants studied in relation to various diseases. Literature indicates that the differentially expressed miRNA-145 in patients’ serum is an essential biomarker for abdominal aortic aneurysm (AAA). However, the correlation between specific miR-145 genetic polymorphisms with AAA susceptibility is inadequately studied.

Materials and Methods: Eighty-seven AAA patients and 122 healthy controls were recruited. Peripheral blood samples were genotyped for miRNA-145 SNPs; rs55945735, rs73798217 and rs353291.

Results: The GG genotype of the rs55945735 polymorphism (p=0.047) and the AG genotype of the rs353291 polymorphism (p=0.036) were overrepresented in AAA patients compared to healthy individuals, revealing an association with susceptibility to AAA development.

Conclusion: SNPs rs55945735 and rs353291 are associated with AAA susceptibility.

Keywords: Abdominal aortic aneurysms, miRNAs, rs55945735, rs353291, rs73798217, miRNA-145

Abdominal aortic aneurysm (AAA) affects 1-2% of all 65-year-​old men and 0.5% of 70-year-​old women (1-3). During AAA formation, the aortic wall gradually weakens and becomes thicker, due to oxidative stress, aortic wall inflammation, collagen and elastin proteolysis and apoptosis of smooth muscle cells (4). Treatment of AAA aims to prevent rupture and currently includes endovascular or open surgical repair. These procedures are associated with considerable perioperative and postoperative risks (5-8).

Early diagnosis of AAA is of utmost importance in reducing the incidence of rupture. Predicting the progression rate of small AAAs and estimating the risk of rupture is also very important in preventing rupture of AAAs (3). Discovering new prognostic and diagnostic methods for the early stages of AAA disease is therefore crucial. Several studies have revealed interesting biomarkers in order to detect early-stage AAA disease, such as D- dimer, fibrinogen and thrombin – antithrombin III complex (9). Other blood molecules that may be involved in AAA formation and can be used as biomarkers as well, include matrix metalloproteinases, lipids, acute-phase reactants, and inflammatory molecules (10-11).

The use of miRNAs as biomarkers has been studied in various pathological conditions, including cancer and cardiovascular diseases (12-14). MicroRNAs are small, non-coding RNA molecules of ~23 nucleotides length (15) exerting regulation in post-transcriptional gene expression and cell cycle events in response to cellular or environmental changes (16-18). Several miRNAs are expressed to the smooth muscle cells of the aorta and are pivotal for regulating their proliferation and differentiation. MiRNA-145 plays a significant role to the multipotent cardiac progenitor cell fate directing the differentiation to cardiac and vascular smooth muscle cells (19-21). MiRNA-145 is abundant in the vascular wall of the arteries; however, in pathological conditions like AAA, a significant decrease of miRNA-145 in vascular walls has been noticed (22). Data from both experimental and clinical studies suggest that miRNA-145 differentiated levels in patients’ serum could serve as an essential biomarker for AAA detection and progression (23).

Single nucleotide polymorphisms (SNPs) in miRNA genes (miR-SNPs) could affect miRNA function via either altering transcription of the primary miRNA transcript, or processing of the pri-miRNA and pre-miRNA or by influencing miRNA-mRNA interactions (24-27); thus, miR-SNPs are implicated in the development of various diseases (28,29). Although a possible link between miRNA-145 and AAA has been indicated, there is no published data regarding the association of miRNA-145 genetic polymorphisms with AAA susceptibility. Of note, most evidence suggesting the correlation between miRNAs and AAA originates from studies examining aneurysmal and healthy aortic tissue; thus, the need for non-invasive biomarkers remains urgent. Assuming that SNPs in miRNA-145 would exert an alteration in functional capacity of miRNA-145, the present study aimed to evaluate whether the polymorphisms rs55945735, rs353291 and rs73798217 detected in whole blood samples might be implicated in AAA disease.

Materials and Methods

Eighty-seven patients diagnosed with AAA and 122 healthy individuals participated in the study. All enrolled patients were hospitalized in a single center institution. Peripheral blood samples from both patients and healthy participants were transferred and stored at –80˚C at the Biology Laboratory of the Athens School of Medicine. Each individual signed an informed consent before participating to the study. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Hospital Ethics committee. Table I shows the data concerning the demographic and clinical parameters of our patients.

Table I. Demographics and clinical characteristics of patients participating in our study.

graphic file with name in_vivo-36-1121-i0001.jpg

Open in a new tab

Genotyping. Genomic DNA was extracted from peripheral blood samples using the Nucleospin Blood Kit (MACHEREY-NAGEL GmbH & Co. KG, Düren, Germany) according to the manufacturer’s instructions. PCR-RFLP assay and gel electrophoresis were performed to evaluate 2 SNPs: rs55945735 (A>G) and rs353291 (A>G). PCR products were subjected to restriction enzyme digestion to confirm the presence/absence of the mutation. Allele specific PCR was performed to evaluate the SNP rs73798217 (G>A). All primers set, PCR conditions and restriction enzymes used are presented in Table II.

Table II. Primer sequences and digestion products.

graphic file with name in_vivo-36-1122-i0001.jpg

Open in a new tab

Statistical analysis. Statistical analysis was performed by GraphPad PRISM (version 3.00; GraphPad Software, San Diego, CA, USA). Genotype frequencies were compared with the Fisher’s exact test with Yate’s correction using S-Plus (v.6.2 Insightful, Seattle, WA, USA). Odds ratios (OR) and 95% CI were obtained with GraphPad (version 3.00; GraphPad Software). The Hardy-Weinberg equilibrium was verified by calculating the expected frequencies and numbers and was tested separately in patients and controls using the goodness-of-fit χ2 test. The p-values are all 2-sided. p-Values of <0.05 were considered significant.

Results

Samples from AAA patients (n=87) and healthy individuals (n=122) that served as control group were collected and analyzed; genotypes and allele distribution for the rs55945735, rs73798217 and rs353291 polymorphisms are presented in Table III. The GG genotype of the rs55945735 polymorphism and the AG genotype of the rs353291 polymorphism, were found over-represented in AAA patients compared to healthy individuals (p=0.047; OR=2.646, 95% CI=1.102-6.355 and p=0.036; OR=3.221, 95% CI=1.039-9.988), revealing a significant association of these SNPs with susceptibility to AAA development. No statistically significant difference was found in genotype and allele frequency distribution regarding the rs55945735 and the rs353291 polymorphisms. Considering the genotyping of rs73798217 polymorphism, outcomes show that the heterozygous AG genotype might suggest a possible protective role against AAA, although results were of borderline significance (p=0.0533; OR=0.1863, 95% CI=0.03580-0.96920).

Table III. Single-nucleotide polymorphism distribution.

graphic file with name in_vivo-36-1122-i0002.jpg

Open in a new tab

Discussion

AAA is a life-threatening condition of multifactorial aetiology affected by both genetic and environmental stimuli. Development and progression of AAAs are connected with inflammation, extracellular matrix degradation and the apoptotic cell death of vascular smooth muscle cells. Experiments with specific SMCs highlight the importance of miRNAs for homeostasis of vascular SMCs (30). AAAs are characterized by malfunction of vascular SMCs and it is therefore possible that miRNAs might have a role in AAA genesis (31). MiRNA-145 has been known to be of key importance in a plethora of malignancies, prostate, lung, gastrointestinal and breast cancer (32). Beyond cancer biogenesis and progression, miRNA-145 has also been shown to be the most abundant miRNA in vascular walls and in isolated VSMCs. MiRNA expression in AAA has been significant dysregulated, but results of different studies for most miRNAs are contradicting (33-37). MiRNA-143/145 cluster is well characterized in vascular disease models reporting a dramatic reduction, e.g., carotid balloon/wire injury, carotid ligation in rats, and in ApoE-/- mice (22,38,39). Moreover, human study data indicate downregulation of miR-145 in plasma and tissue samples of vascular disease patients including thoracic aortic dissection (40), thoracic aortic aneurysm (41) and abdominal aortic aneurysms (42,43). Controversially, Stather et al. found that the expression of miRNA-145 between AAA and controls does not differ (44), while Pei et al. found an up-regulation in excised aneurysmal tissues (45). Apart from abdominal aortic aneurysms, miRNA-145 upregulation has also been linked to other types of aneurysms such as intracranial (46).

The biological function of miRNA-145 in AAA is not well understood. MiRNA-145 has been repeatedly shown to trigger SMC differentiation and inhibit SMC proliferation (22,39). It may also have a negative impact on the contractile SMC phenotype (29-32) and may possibly contribute to a dysfunctional matrix-cell unit and weakened vessel integrity (42).

Few data in the literature support that miRNA-145 may play an important role for aneurysm formation and development. Οver-expression of miRNA-145 by lentivirus infection greatly decreased AAA incidence, maximum abdominal aortic diameter, and elastin degradation, accompanied with MMP2 activation downregulation in AngII-infused ApoE-/- mice (47). Lovren and colleagues reported a miRNA-145 treatment targeting SMCs, which notably increased collagen content in atherosclerotic plaque (48). Downregulation of miRNA-145 via knock-down of Dicer in a mouse model led to reduced thickness of the aortic medium, associated with reduced SMC differentiation (30). On the other hand, miRNA-145 expression was found to be increased in ascending aortic aneurysm tissue compared to the aortic tissue of healthy controls (45).

Despite the above data, the molecular mechanisms leading to dysregulated expression of miRNA-145 are still unclear. SNPs could be an important factor for miRNA-145 regulation; thus, we aimed to evaluate whether the polymorphisms rs55945735, rs353291 and rs73798217 detected in whole blood samples are implicated in the development and the progression of AAA. Our findings could potentially help to provide further knowledge on these mechanisms, although a functional validation on AAA samples is also needed (29). In our study, the frequency of three different SNPs located in miRNA-145 gene was evaluated in order to elucidate whether there is a connection between these polymorphisms and AAA susceptibility in the Greek patient population. As far as we know, these SNPs have not been studied in cardiovascular diseases, but there are only data to show their association with other disease susceptibility like cancer (29).

Our data suggest that additional SNPs (rs55945735 and rs353291) could influence the development of AAA. More specifically, the mutant homozygotes of the rs55945735 and the heterozygotes of the rs353291, were found overrepresented in AAA patients’ group compared to healthy controls, which indicates a strong correlation of these SNPs with susceptibility to AAA development. To the best of our knowledge, this is the first study that reports the presence of an association between miRNA-145 gene polymorphisms and AAA. Chacon-Cortes et al. (29) investigated the association of these SNPs with breast cancer development concluding that rs353291 may be a genetic risk factor. On the other hand, no statistically significant difference in allelic or genotype frequencies of rs55945735 were revealed between breast cancer patients and healthy controls; however, the authors highlight that these findings must be considered in light of some limitations as their study population consisted only of female patients.

Concerning the rs73798217, no significant differences in the distribution of genotype and allele frequencies were observed between AAA patients and the control group. Therefore, this genetic variant seems not to influence the risk of AAA development in our population. Similarly, other studies found no association of rs73798217 with breast cancer and hydrosalpinx-induced defective endometrial receptivity, implying that its role may not be crucial for miRNA-145 functionality.

In conclusion, the results of the present study show that overexpression of miRNA-145 SNPs rs55945735 and rs353291 may be associated with the risk of AAA development and progression, indicating a theoretical basis for AAA treatment and detection. Further studies are required in order to elucidate whether these polymorphisms lead to an abnormal expression of miRNA-145 in AAA revealing potential pathways of AAA development and progression.

Conflicts of Interest

The Authors declare no conflicts of interest in relation to this study.

Authors’ Contributions

Conceptualization: M.G, C.K., A.K.; methodology: N.H., N.P.A.; validation: M.G., E.L.; formal analysis: E.L., N.P.A.; writing—original draft preparation: N.P.A. E.L., N.H.; writing—review and editing: M.G., C.K. All Authors have read and agreed to the published version of the manuscript.

References

  • 1.Sakalihasan N, Michel JB, Katsargyris A, Kuivaniemi H, Defraigne JO, Nchimi A, Powell JT, Yoshimura K, Hultgren R. Abdominal aortic aneurysms. Nat Rev Dis Primers. 2018;4(1):34. doi: 10.1038/s41572-018-0030-7. [DOI] [PubMed] [Google Scholar]
  • 2.Ouriel K, Green RM, Donayre C, Shortell CK, Elliott J, DeWeese JA. An evaluation of new methods of expressing aortic aneurysm size: relationship to rupture. J Vasc Surg. 1992;15(1):12–8. doi: 10.1067/mva.1992.32982. discussion 19-20. [DOI] [PubMed] [Google Scholar]
  • 3.Patel MI, Hardman DT, Fisher CM, Appleberg M. Current views on the pathogenesis of abdominal aortic aneurysms. J Am Coll Surg. 1995;181(4):371–382. [PubMed] [Google Scholar]
  • 4.Nordon IM, Hinchliffe RJ, Loftus IM, Thompson MM. Pathophysiology and epidemiology of abdominal aortic aneurysms. Nat Rev Cardiol. 2011;8(2):92–102. doi: 10.1038/nrcardio.2010.180. [DOI] [PubMed] [Google Scholar]
  • 5.Hallin A, Bergqvist D, Holmberg L. Literature review of surgical management of abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 2001;22(3):197–204. doi: 10.1053/ejvs.2001.1422. [DOI] [PubMed] [Google Scholar]
  • 6.Cruz CP, Drouilhet JC, Southern FN, Eidt JF, Barnes RW, Moursi MM. Abdominal aortic aneurysm repair. Vasc Surg. 2001;35(5):335–344. doi: 10.1177/153857440103500502. [DOI] [PubMed] [Google Scholar]
  • 7.Turnipseed WD, Carr SC, Tefera G, Acher CW, Hoch JR. Minimal incision aortic surgery. J Vasc Surg. 2001;34(1):47–53. doi: 10.1067/mva.2001.115809. [DOI] [PubMed] [Google Scholar]
  • 8.Cuypers P, Buth J, Harris PL, Gevers E, Lahey R. Realistic expectations for patients with stent-graft treatment of abdominal aortic aneurysms. Results of a European multicentre registry. Eur J Vasc Endovasc Surg. 1999;17(6):507–516. doi: 10.1053/ejvs.1999.0836. [DOI] [PubMed] [Google Scholar]
  • 9.Sidloff DA, Stather PW, Choke E, Bown MJ, Sayers RD. A systematic review and meta-analysis of the association between markers of hemostasis and abdominal aortic aneurysm presence and size. J Vasc Surg. 2014;59(2):528–535.e4. doi: 10.1016/j.jvs.2013.10.088. [DOI] [PubMed] [Google Scholar]
  • 10.Stather PW, Sidloff DA, Dattani N, Gokani VJ, Choke E, Sayers RD, Bown MJ. Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic aneurysm. Br J Surg. 2014;101(11):1358–1372. doi: 10.1002/bjs.9593. [DOI] [PubMed] [Google Scholar]
  • 11.Folsom AR, Yao L, Alonso A, Lutsey PL, Missov E, Lederle FA, Ballantyne CM, Tang W. Circulating biomarkers and abdominal aortic aneurysm incidence: The atherosclerosis risk in communities (ARIC) study. Circulation. 2015;132(7):578–585. doi: 10.1161/CIRCULATIONAHA.115.016537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Legaki E, Siasos G, Klonaris C, Athanasiadis D, Patelis N, Sioziou A, Oikonomou E, Liakakos T, Gazouli M, Tousoulis D. Mir-335-5p as a potential regulator of LRP1 expression in abdominal aortic aneurysm. Hellenic J Cardiol. 2020;61(6):430–432. doi: 10.1016/j.hjc.2020.01.002. [DOI] [PubMed] [Google Scholar]
  • 13.Legaki E, Klonaris C, Athanasiadis D, Patelis N, Sioziou A, Liakakos T, Gazouli M. DAB2IP expression in abdominal aortic aneurysm: EZH2 and mir-363-3p as potential mediators. In Vivo. 2019;33(3):737–742. doi: 10.21873/invivo.11533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Sioziou A, Katifelis H, Legaki E, Patelis N, Athanasiades D, Liakakos T, Klonaris C, Gazouli M. Expression of miR21, miR122, miR146a and miR196 in symptomatic carotid disease. Int Cardiovasc Res J. 2018;12(1):7–12. [Google Scholar]
  • 15.Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–233. doi: 10.1016/j.cell.2009.01.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Reinhart BJ, Bartel DP. Small RNAs correspond to centromere heterochromatic repeats. Science. 2002;297(5588):1831. doi: 10.1126/science.1077183. [DOI] [PubMed] [Google Scholar]
  • 17.Aravin AA, Hannon GJ, Brennecke J. The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science. 2007;318(5851):761–764. doi: 10.1126/science.1146484. [DOI] [PubMed] [Google Scholar]
  • 18.Champeris Tsaniras S, Delinasios GJ, Petropoulos M, Panagopoulos A, Anagnostopoulos AK, Villiou M, Vlachakis D, Bravou V, Stathopoulos GT, Taraviras S. DNA replication inhibitor geminin and retinoic acid signaling participate in complex interactions associated with pluripotency. Cancer Genomics Proteomics. 2019;16(6):593–601. doi: 10.21873/cgp.20162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Leeper NJ, Raiesdana A, Kojima Y, Chun HJ, Azuma J, Maegdefessel L, Kundu RK, Quertermous T, Tsao PS, Spin JM. MicroRNA-26a is a novel regulator of vascular smooth muscle cell function. J Cell Physiol. 2011;226(4):1035–1043. doi: 10.1002/jcp.22422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, Latronico MV, Peterson KL, Indolfi C, Catalucci D, Chen J, Courtneidge SA, Condorelli G. 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(12):1590–1598. doi: 10.1038/cdd.2009.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 2009;460(7256):705–710. doi: 10.1038/nature08195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Cheng Y, Liu X, Yang J, Lin Y, Xu DZ, Lu Q, Deitch EA, Huo Y, Delphin ES, Zhang C. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res. 2009;105(2):158–166. doi: 10.1161/CIRCRESAHA.109.197517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Davis-Dusenbery BN, Wu C, Hata A. Micromanaging vascular smooth muscle cell differentiation and phenotypic modulation. Arterioscler Thromb Vasc Biol. 2011;31(11):2370–2377. doi: 10.1161/ATVBAHA.111.226670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Duan S, Mi S, Zhang W, Dolan ME. Comprehensive analysis of the impact of SNPs and CNVs on human microRNAs and their regulatory genes. RNA Biol. 2009;6(4):412–425. doi: 10.4161/rna.6.4.8830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Sun G, Yan J, Noltner K, Feng J, Li H, Sarkis DA, Sommer SS, Rossi JJ. SNPs in human miRNA genes affect biogenesis and function. RNA. 2009;15(9):1640–1651. doi: 10.1261/rna.1560209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Ryan BM, Robles AI, Harris CC. Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer. 2010;10(6):389–402. doi: 10.1038/nrc2867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Lee HC, Yang CW, Chen CY, Au LC. Single point mutation of microRNA may cause butterfly effect on alteration of global gene expression. Biochem Biophys Res Commun. 2011;404(4):1065–1069. doi: 10.1016/j.bbrc.2010.12.114. [DOI] [PubMed] [Google Scholar]
  • 28.Wang Q, Ai H, Li X, Tian H, Ning B, Zhang M, La X. Association of miRNA-145 with the occurrence and prognosis of hydrosalpinx-induced defective endometrial receptivity. Bosn J Basic Med Sci. 2021;21(1):81–92. doi: 10.17305/bjbms.2020.4538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Chacon-Cortes D, Smith RA, Haupt LM, Lea RA, Youl PH, Griffiths LR. Genetic association analysis of miRNA SNPs implicates MIR145 in breast cancer susceptibility. BMC Med Genet. 2015;16:107. doi: 10.1186/s12881-015-0248-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Albinsson S, Suarez Y, Skoura A, Offermanns S, Miano JM, Sessa WC. MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function. Arterioscler Thromb Vasc Biol. 2010;30(6):1118–1126. doi: 10.1161/ATVBAHA.109.200873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Joviliano EE, Ribeiro MS, Tenorio EJR. MicroRNAs and current concepts on the pathogenesis of abdominal aortic aneurysm. Braz J Cardiovasc Surg. 2017;32(3):215–224. doi: 10.21470/1678-9741-2016-0050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Ye D, Shen Z, Zhou S. Function of microRNA-145 and mechanisms underlying its role in malignant tumor diagnosis and treatment. Cancer Manag Res. 2019;11:969–979. doi: 10.2147/CMAR.S191696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Boon RA, Seeger T, Heydt S, Fischer A, Hergenreider E, Horrevoets AJ, Vinciguerra M, Rosenthal N, Sciacca S, Pilato M, van Heijningen P, Essers J, Brandes RP, Zeiher AM, Dimmeler S. MicroRNA-29 in aortic dilation: implications for aneurysm formation. Circ Res. 2011;109(10):1115–1119. doi: 10.1161/CIRCRESAHA.111.255737. [DOI] [PubMed] [Google Scholar]
  • 34.Pahl MC, Derr K, Gäbel G, Hinterseher I, Elmore JR, Schworer CM, Peeler TC, Franklin DP, Gray JL, Carey DJ, Tromp G, Kuivaniemi H. MicroRNA expression signature in human abdominal aortic aneurysms. BMC Med Genomics. 2012;5:25. doi: 10.1186/1755-8794-5-25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Hergenreider E, Heydt S, Tréguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, Braun T, Urbich C, Boon RA, Dimmeler S. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol. 2012;14(3):249–256. doi: 10.1038/ncb2441. [DOI] [PubMed] [Google Scholar]
  • 36.Araujo NNF, Lin-Wang HT, Germano JF, Farsky PS, Feldman A, Rossi FH, Izukawa NM, Higuchi ML, Savioli Neto F, Hirata MH, Bertolami MC. Dysregulation of microRNAs and target genes networks in human abdominal aortic aneurysm tissues. PLoS One. 2019;14(9):e0222782. doi: 10.1371/journal.pone.0222782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Wanhainen A, Mani K, Vorkapic E, De Basso R, Björck M, Länne T, Wågsäter D. Screening of circulating microRNA biomarkers for prevalence of abdominal aortic aneurysm and aneurysm growth. Atherosclerosis. 2017;256:82–88. doi: 10.1016/j.atherosclerosis.2016.11.007. [DOI] [PubMed] [Google Scholar]
  • 38.Boettger T, Beetz N, Kostin S, Schneider J, Krüger M, Hein L, Braun T. Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest. 2009;119(9):2634–2647. doi: 10.1172/JCI38864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 2009;460(7256):705–710. doi: 10.1038/nature08195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Liao M, Zou S, Weng J, Hou L, Yang L, Zhao Z, Bao J, Jing Z. 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(5):1341–1349.e3. doi: 10.1016/j.jvs.2010.11.113. [DOI] [PubMed] [Google Scholar]
  • 41.Ikonomidis JS, Ivey CR, Wheeler JB, Akerman AW, Rice A, Patel RK, Stroud RE, Shah AA, Hughes CG, Ferrari G, Mukherjee R, Jones JA. Plasma biomarkers for distinguishing etiologic subtypes of thoracic aortic aneurysm disease. J Thorac Cardiovasc Surg. 2013;145(5):1326–1333. doi: 10.1016/j.jtcvs.2012.12.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Venkatesh P, Phillippi J, Chukkapalli S, Rivera-Kweh M, Velsko I, Gleason T, VanRyzin P, Aalaei-Andabili SH, Ghanta RK, Beaver T, Chan EKL, Kesavalu L. Aneurysm-specific miR-221 and miR-146a participates in human thoracic and abdominal aortic aneurysms. Int J Mol Sci. 2017;18(4):875. doi: 10.3390/ijms18040875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Zhang W, Shang T, Huang C, Yu T, Liu C, Qiao T, Huang D, Liu Z, Liu C. Plasma microRNAs serve as potential biomarkers for abdominal aortic aneurysm. Clin Biochem. 2015;48(15):988–992. doi: 10.1016/j.clinbiochem.2015.04.016. [DOI] [PubMed] [Google Scholar]
  • 44.Stather PW, Sylvius N, Sidloff DA, Dattani N, Verissimo A, Wild JB, Butt HZ, Choke E, Sayers RD, Bown MJ. Identification of microRNAs associated with abdominal aortic aneurysms and peripheral arterial disease. Br J Surg. 2015;102(7):755–766. doi: 10.1002/bjs.9802. [DOI] [PubMed] [Google Scholar]
  • 45.Pei H, Tian C, Sun X, Qian X, Liu P, Liu W, Chang Q. Overexpression of microRNA-145 promotes ascending aortic aneurysm media remodeling through TGF-β1. Eur J Vasc Endovasc Surg. 2015;49(1):52–59. doi: 10.1016/j.ejvs.2014.10.018. [DOI] [PubMed] [Google Scholar]
  • 46.Liao B, Zhou MX, Zhou FK, Luo XM, Zhong SX, Zhou YF, Qin YS, Li PP, Qin C. Exosome-derived MiRNAs as biomarkers of the development and progression of intracranial aneurysms. J Atheroscler Thromb. 2020;27(6):545–610. doi: 10.5551/jat.51102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Wu J, Wang J, Li X, Liu X, Yu X, Tian Y. MicroRNA-145 mediates the formation of angiotensin II-induced murine abdominal aortic aneurysm. Heart Lung Circ. 2017;26(6):619–626. doi: 10.1016/j.hlc.2016.10.009. [DOI] [PubMed] [Google Scholar]
  • 48.Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta N, Steer BM, Ingram AJ, Gupta M, Al-Omran M, Teoh H, Marsden PA, Verma S. MicroRNA-145 targeted therapy reduces atherosclerosis. Circulation. 2012;126(11 Suppl 1):S81–S90. doi: 10.1161/CIRCULATIONAHA.111.084186. [DOI] [PubMed] [Google Scholar]

Articles from In Vivo are provided here courtesy of International Institute of Anticancer Research

RESOURCES