Potential of circulating pro-angiogenic microRNA expressions as biomarkers for rapid angiographic stenotic progression and restenosis risks in coronary artery disease patients underwent percutaneous coronary intervention

Abstract

Background: This study aimed to investigate the correlation of pro-angiogenic microRNA (miRNA) expressions with rapid angiographic stenotic progression (RASP) and restenosis risks in coronary artery disease (CAD) patients underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES).

Methods: A total of 286 CAD patients underwent PCI with DES were consecutively recruited in this study. Plasma samples were collected before PCI operation, and 14 pro-angiogenic miRNAs were measured by real-time quantitative reverse transcription-polymerase chain reaction. Rapid angiographic stenotic progression at nontarget lesions and restenosis at stented lesions were evaluated by quantitative coronary angiography at 12 months after PCI operation.

Results: The occurrence rates of RASP and restenosis were 39.5% and 22.4%, respectively. Let-7f, miR-19a, miR-19b-1, miR-92a, miR-126, miR-210, and miR-296 were decreased in RASP patients than non-RASP patients, among which let-7f, miR-19a, miR-126, miR-210, and miR-296 independently correlated with lower RASP occurrence by multivariate analysis, followed by receiver-operating characteristic (ROC) curve exhibited that these five miRNAs showed great value in predicting RASP risk with area under curve (AUC) 0.879 (95% CI: 0.841-0.917). Besides, let-7f, miR-19a, miR-92a, miR-126, miR-130a, and miR-210 were reduced in restenosis patients than non-restenosis patients, among them miR-19a, miR-126, miR-210, and miR-378 independently correlated with lower restenosis occurrence by multivariate analysis, followed by ROC curve disclosed that these four miRNAs had good value in predicting restenosis risk with AUC 0.776 (95% CI: 0.722-0.831).

Conclusions: Circulating let-7f, miR-19a, miR-126, miR-210, and miR-296 independently correlate with reduced RASP risk, while miR-19a, miR-126, miR-210, and miR-378 independently correlate with decreased restenosis risk in CAD patients underwent PCI with DES.

Keywords: coronary artery disease; percutaneous coronary intervention; pro-angiogenesis microRNA; rapid angiographic stenotic progression; restenosis.

Figure 1

Study flow

Figure 2

RASP and restenosis occurrence. The occurrence rate of RASP and restenosis was 39.5% and 22.4%, respectively. RASP, rapid angiographic stenotic progression

Figure 3

Pro‐angiogenic miRNA expression levels in RASP and non‐RASP patients. Lower baseline expression levels of let‐7f (B), miR‐19a (F), miR‐19b‐1 (G), miR‐92a (I), miR‐126 (J), miR‐210 (L), and miR‐296 (M) were observed in RASP patients compared with non‐RASP patients, while no difference in the other seven miRNA expression levels (including let‐7b (A), miR‐17‐5p (C), miR‐17‐3p (D), miR‐18a (E), miR‐20a (H), miR‐130a (K), and miR‐378 (N)) at baseline was discovered between RASP patients and non‐RASP patients. Comparison was determined by the Wilcoxon rank‐sum test. P < .05 was considered as significant. miRNA, microRNA; RASP, rapid angiographic stenotic progression

Figure 4

ROC curve analysis for RASP risk. ROC curve disclosed that let‐7f, miR‐19a, miR‐126, miR‐210, and miR‐296 could predict RASP risk, and combination of all these five miRNAs presented even better predictive value for RASP occurrence (red color line). The analysis was determined by ROC curve analysis. RASP, rapid angiographic stenotic progression; ROC, receiver‐operating characteristic

Figure 5

Pro‐angiogenic miRNA expression levels in restenosis and non‐restenosis patients. Decreased baseline expression levels of let‐7f (B), miR‐19a (F), miR‐92a (I), miR‐126 (J), miR‐130a (K), and miR‐210 (L) were observed in restenosis patients compared with non‐restenosis patients, while no difference in the other eight miRNA expression levels (including let‐7b (A), miR‐17‐5p (C), miR‐17‐3p (D), miR‐18a (E), miR‐19b‐1 (G), miR‐20a (H), miR‐296 (M), and miR‐378 (N)) at baseline was discovered between restenosis patients and non‐restenosis patients. Comparison was determined by the Wilcoxon rank‐sum test. P < .05 was considered as significant. miRNA, microRNA

Figure 6

ROC curve analysis for restenosis risk. ROC curve revealed that miR‐19a, miR‐126, and miR‐210 could predict restenosis risk, while miR‐378 could not, and combination of all these four miRNAs displayed good predictive value for restenosis occurrence (red color line). The analysis was determined by ROC curve analysis. miRNA, microRNA; ROC, receiver‐operating characteristic