Expression of Plasma Levels of miRNA-181b and miRNA-21 in Patients With Abdominal Aortic Aneurysms and Their Effect on Clinical Outcome After Endovascular Treatment

Abstract

Introduction:

Abdominal aortic aneurysms (AAA) are major causes of morbidity and mortality in the elderly population. Endovascular aneurysm repair (EVAR) is associated with lower complications rates than conventional treatment; however, rigorous follow-up with contrast imaging is required to confirm aneurysmal sac exclusion. The main objective of this study was to quantify and evaluate miRNA expression response to EVAR based on serum dosages at the 6-month follow-up.

Population and Method:

47 patients with indication for EVAR were recruited and 10 patients without comorbidities. miRNA-181b and miRNA-21 were selected for this study and their serum dosages were measured at two time points: preoperatively and after 6 months of follow-up, and only once in the control group. Demographic profiles, clinical follow-ups, and imaging examinations with angiotomography performed preoperatively and after 6 months were collected.

Results:

Overexpression of miRNA-181b and miRNA-21 was observed in the whole blood of patients with AAA. EVAR of patients with AAA resulted in decreased expression of the studied miRNAs, indicating that exclusion of the aneurysmal sac alters the expression of these markers. In addition, the expressions of miRNAs did not correlate with endoleaks or the diameter of the aneurysm or with the different types of devices used for the EVAR.

Conclusions:

The overexpression of miRNA-181b, miRNA-21 with its reduction after EVAR, may suggest the use of these molecules as potential biomarkers in the follow-up of these patients. However, miRNAs were not able to identify possible endoleaks or discriminate them into subtypes.

Clinical Impact

The clinical application of the use of biomarkers in other areas such as oncology is already well established. In endovascular surgery it is still incipient although with great potential in daily practice, in order to anticipate or schedule possible interventions in patients with endoleak. In addition, understand the mechanisms of action of miRNAs in Atherosclerotic diseases and aortic syndromes could provide a better understanding of the pathophysiology as well as pharmacological development for AAA prevention as well as remodeling of the aneurysm sac after EVAR.

Keywords

abdominal aortic aneurysm EVAR microRNAs biomarkers endoleaks

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References

Norman

Powell

JT.

Site specificity of aneurysmal disease. Circulation. 2010;121(4):560–568.

Sakalihasan

Limet

Defawe

Abdominal aortic aneurysm. The Lancet. 2005;365(9470):1577–1589.

Tenorio

EJR

Braga

AFF

Tirapelli

DPDC

, et al 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;50:209–217.

Ali

Fitzpatrick-Lewis

Miller

, et al Screening for abdominal aortic aneurysm in asymptomatic adults. J Vasc Surg. 2016;64(6):1855–1868. Accessed February 11, 2020. https://www.sciencedirect.com/science/article/pii/S074152141630828X

Blanchard

JF.

Epidemiology of abdominal aortic aneurysms. Epidemiol Rev. 1999;21(2):207–221.

Humberto

Complicações do tratamento endovascular do aneurisma de aorta abdominal. In: Humberto

, ed. Doenças Vasculares Periféricas. Rio de Janeiro: Guanabara Koogan; 2016:1493–1509.

Morris

Golledge

The association between plasma matrix metalloproteinase-9 concentration and endoleak after endovascular aortic aneurysm repair: a meta-analysis. Atherosclerosis. 2015;242(2):535–542. Accessed February 28, 2024. https://pubmed.ncbi.nlm.nih.gov/26302168/

Hovsepian

Ziporin

Sakurai

, et al Elevated plasma levels of matrix metalloproteinase-9 in patients with abdominal aortic aneurysms: a circulating marker of degenerative aneurysm disease. J Vasc Interv Radiol. 2000;11(10):1345–1352.

Hellenthal

FAMVI

Ten Bosch

Pulinx

, et al Plasma levels of matrix metalloproteinase-9: a possible diagnostic marker of successful endovascular aneurysm repair. Eur J Vasc Endovasc Surg. 2012;43(2):171–172.

10.

Zhang

, et al Roles and mechanisms of miRNAs in abdominal aortic aneurysm: signaling pathways and clinical insights. Curr Atheroscler Rep. 2024;26(7):273–287.

11.

Small

Frost

RJA

Olson

EN.

MicroRNAs add a new dimension to cardiovascular disease. Circulation. 2010;121(8):1022–1032.

12.

Krek

Grün

Poy

, et al Combinatorial microRNA target predictions. Nat Genet. 2005;37(5):495–500.

13.

Wanhainen

Mani

Vorkapic

, et al Screening of circulating microRNA biomarkers for prevalence of abdominal aortic aneurysm and aneurysm growth. Atherosclerosis. 2017;256:82–88.

14.

Schurink

Aarts

Wilde

, et al Endoleakage after stent-graft treatment of abdominal aneurysm: implications on pressure and imaging—an in vitro study. J Vasc Surg. 1998; 28(2):234–241.

15.

Balm

Jacobs

MJ.

Use of spiral computed tomographic angiography in monitoring abdominal aortic aneurysms after transfemoral endovascular repair. Tex Heart Inst J. 1997;24(3):200–203.

16.

Karch

Henretta

Hodgson

, et al Algorithm for the diagnosis and treatment of endoleaks. Am J Surg. 1999; 178(3):225–231.

17.

Maegdefessel

Dalman

Tsao

PS.

Pathogenesis of abdominal aortic aneurysms: microRNAs, proteases, genetic associations. Annu Rev Med. 2014;65:49–62.

18.

Cui

Zhang

, et al Effect of miR-21 on rat thoracic aortic aneurysm model by regulating the expressions of MMP-2 and MMP-9. Eur Rev Med Pharmacol Sci. 2020;24(2):878–884.

19.

Huang

Yue

, et al MicroRNA-21 knockout exacerbates angiotensin II–induced thoracic aortic aneurysm and dissection in mice with abnormal transforming growth factor-β–SMAD3 signaling. Arterioscler Thromb Vasc Biol. 2018;38(5):1086–1101.

20.

Maegdefessel

Azuma

Toh

, et al MicroRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented expansion. Sci Transl Med. 2012;4(122):122ra22. Accessed March 16, 2021. https://stm.sciencemag.org/content/4/122/122ra22?_ga=2.232071709.306203391.1615898964-413702062.1615898964

21.

Kumar

Boon

Maegdefessel

, et al Role of noncoding RNAs in the pathogenesis of abdominal aortic aneurysm. Circ Res. 2019;124(4):619–630.

22.

Missae

Rossoni

Tenorio

EJR

, et al 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(3):301–307.

23.

Di Gregoli

Anuar

NNM

Bianco

, et al MicroRNA-181b controls atherosclerosis and aneurysms through regulation of TIMP-3 and elastin. Circ Res. 2017;120(1):49–65.

24.

Hou

Yang

Zheng

Licochalcone a attenuates abdominal aortic aneurysm induced by angiotensin II via regulating the miR-181b/SIRT1/HO-1 signaling. J Cell Physiol. 2018; 234(5):7560–7568.

25.

Fry

Al Sayah

Weisbrod

, et al Vascular smooth muscle sirtuin-1 protects against diet-induced aortic stiffness. Hypertension. 2016;68(3):775–784.

26.

Schurink

Aarts

van Bockel

JH.

Endoleak after stent-graft treatment of abdominal aortic aneurysm: a meta-analysis of clinical studies. Br J Surg. 1999;86(5):581–587.

27.

Zarins

White

Hodgson

, et al Endoleak as a predictor of outcome after endovascular aneurysm repair: AneuRx multicenter clinical trial. J Vasc Surg. 2000;32(1):90–107.

28.

Cuypers

Buth

Harris

, et al 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.