Circulating MicroRNAs As Potential Biomarkers for Cerebral Collateral Circulation in Symptomatic Carotid Stenosis

Overview

Journal Front Physiol

Date 2024 Nov 18

PMID 39552721

Authors

Wenwen Liang

Bingcang Huang

Qin Shi

Xuelian Yang

Hanwen Zhang

Wei Chen

Affiliations

Soon will be listed here.

Abstract

Background: Cerebral collateral circulation (CCC) considerably improves the prognosis of patients with symptomatic carotid stenosis (SCS). This study evaluated the diagnostic value of plasma microRNAs (miRNAs) in determining CCC status in patients with SCS.

Methods: This single-center observational study enrolled patients with ≥50% carotid artery stenosis diagnosed using Doppler ultrasound. CCC was assessed using cerebrovascular digital subtraction angiography (DSA). Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of plasma miRNAs. A multivariate logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the diagnostic value of plasma miRNA expression in determining CCC status.

Results: A total of 43 patients were enrolled (28 with CCC and 15 without CCC). The plasma expression levels of miR-126-3p, miR-132-3p, and miR-210-3p were significantly higher and those of miR-16-3p and miR-92-3p were significantly lower in patients with CCC. After adjusting for age, gender, drinking history, comorbidities and degree of SCS, miR-92a-3p, miR-126-3p, miR-132-3p, and miR-210-3p were found to be significantly associated with CCC establishment ( < 0.05). ROC curve analysis indicated a high diagnostic value of these miRNAs in determining CCC status [area under the curve (AUC): 0.918-0.965], with miR-126-3p exhibiting the highest predictive performance (AUC: 0.965). Subgroup analysis revealed that patients with CCC who had 50%-70% stenosis showed significantly higher expression level of miR-126-3p, whereas those with CCC who had 70%-99% stenosis showed significantly higher expression levels of miR-126-3p, miR-132-3p, and miR-210-3p as well as significantly lower expression levels of miR-15a-3p, miR-16-3p, and miR-92a-3p.

Conclusion: The results indicate that these six plasma miRNAs have promising diagnostic value in determining CCC status in varying degrees of SCS. These miRNAs can serve as biomarkers for CCC status following SCS, with miR-126-3p showing the strongest positive correlation.

References

Martinez-Arroyo O, Ortega A, Flores-Chova A, Sanchez-Garcia B, Garcia-Garcia A, Chaves F . High miR-126-3p levels associated with cardiovascular events in a general population. Eur J Intern Med. 2023; 113:49-56. PMC: 10271715. DOI: 10.1016/j.ejim.2023.04.013. View

Zeller T, Keller T, Ojeda F, Reichlin T, Twerenbold R, Tzikas S . Assessment of microRNAs in patients with unstable angina pectoris. Eur Heart J. 2014; 35(31):2106-14. DOI: 10.1093/eurheartj/ehu151. View

van Solingen C, Bijkerk R, de Boer H, Rabelink T, van Zonneveld A . The Role of microRNA-126 in Vascular Homeostasis. Curr Vasc Pharmacol. 2013; 13(3):341-51. DOI: 10.2174/15701611113119990017. View

Ma T, Chen Y, Chen Y, Meng Q, Sun J, Shao L . MicroRNA-132, Delivered by Mesenchymal Stem Cell-Derived Exosomes, Promote Angiogenesis in Myocardial Infarction. Stem Cells Int. 2018; 2018:3290372. PMC: 6151206. DOI: 10.1155/2018/3290372. View

Fasanaro P, DAlessandra Y, Stefano V, Melchionna R, Romani S, Pompilio G . MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem. 2008; 283(23):15878-83. PMC: 3259646. DOI: 10.1074/jbc.M800731200. View

Barnett H, Taylor D, Haynes R, Sackett D, Peerless S, Ferguson G . Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991; 325(7):445-53. DOI: 10.1056/NEJM199108153250701. View

Anand S, Majeti B, Acevedo L, Murphy E, Mukthavaram R, Scheppke L . MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat Med. 2010; 16(8):909-14. PMC: 3094020. DOI: 10.1038/nm.2186. View

Liu L, Ding J, Leng X, Pu Y, Huang L, Xu A . Guidelines for evaluation and management of cerebral collateral circulation in ischaemic stroke 2017. Stroke Vasc Neurol. 2018; 3(3):117-130. PMC: 6169613. DOI: 10.1136/svn-2017-000135. View

Heck D, Jost A . Carotid stenosis, stroke, and carotid artery revascularization. Prog Cardiovasc Dis. 2021; 65:49-54. DOI: 10.1016/j.pcad.2021.03.005. View

10.

Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A . MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009; 324(5935):1710-3. DOI: 10.1126/science.1174381. View

11.

Rani V, Sengar R . Biogenesis and mechanisms of microRNA-mediated gene regulation. Biotechnol Bioeng. 2022; 119(3):685-692. DOI: 10.1002/bit.28029. View

12.

Zhou B . Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci. 2002; 15(1):83-96. View

13.

Maguida G, Shuaib A . Collateral Circulation in Ischemic Stroke: An Updated Review. J Stroke. 2023; 25(2):179-198. PMC: 10250877. DOI: 10.5853/jos.2022.02936. View

14.

Svec D, Tichopad A, Novosadova V, Pfaffl M, Kubista M . How good is a PCR efficiency estimate: Recommendations for precise and robust qPCR efficiency assessments. Biomol Detect Quantif. 2016; 3:9-16. PMC: 4822216. DOI: 10.1016/j.bdq.2015.01.005. View

15.

Li H, Zhang P, Li F, Yuan G, Wang X, Zhang A . Plasma miR-22-5p, miR-132-5p, and miR-150-3p Are Associated with Acute Myocardial Infarction. Biomed Res Int. 2019; 2019:5012648. PMC: 6507259. DOI: 10.1155/2019/5012648. View

16.

Faizy T, Mlynash M, Kabiri R, Christensen S, Kuraitis G, Mader M . The Cerebral Collateral Cascade: Comprehensive Blood Flow in Ischemic Stroke. Neurology. 2022; 98(23):e2296-e2306. DOI: 10.1212/WNL.0000000000200340. View

17.

Xu K, Chen C, Wu Y, Wu M, Lin L . Advances in miR-132-Based Biomarker and Therapeutic Potential in the Cardiovascular System. Front Pharmacol. 2021; 12:751487. PMC: 8594750. DOI: 10.3389/fphar.2021.751487. View

18.

Loyer X, Potteaux S, Vion A, Guerin C, Boulkroun S, Rautou P . Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ Res. 2013; 114(3):434-43. DOI: 10.1161/CIRCRESAHA.114.302213. View

19.

Zhao Z, Sun W, Guo Z, Zhang J, Yu H, Liu B . Mechanisms of lncRNA/microRNA interactions in angiogenesis. Life Sci. 2019; 254:116900. DOI: 10.1016/j.lfs.2019.116900. View

20.

Chen J, Cui C, Yang X, Xu J, Venkat P, Zacharek A . MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke. Transl Stroke Res. 2017; 8(4):374-385. PMC: 5604242. DOI: 10.1007/s12975-017-0520-z. View