Predictive value of using plasma long non‑coding RNAs ANRIL and HOXA11‑AS for in‑stent restenosis

Abstract

In-stent restenosis (ISR) can pose serious challenges for cardiologists following coronary stent implantation. Early identification of patients at high risk of ISR is considered to be effective for its prevention. However, factors that can reliably predict the risk of ISR remain elusive at present. The present study aimed to investigate the possible association between plasma long non-coding RNA (lncRNA) levels and ISR. A total of 410 patients with single-vessel lesion who received drug-eluting stents (DES) were included in the present study. After 12-36 months of follow-up, coronary angiography was performed and ISR was defined as >50% diameter stenosis at follow-up. RT-qPCR was used to measure lncRNA expression. Expression of the lncRNA RNA antisense non-coding RNA at the INK4 locus (ANRIL) was found to be upregulated whereas the lncRNA homeobox A11 antisense (HOXA11-AS) was downregulated in the plasma of patients with ISR compared with that from patients without ISR (P<0.001). Logistic regression analysis revealed that ANRIL [odds ratio (OR)=2.95; 95% confidence interval (CI)=1.68-8.08] was an independent risk factor for ISR, whilst HOXA11-AS (OR= 0.58; 95% CI= 0.48-0.71) was found to be an independent protective factor for ISR. Receiver operating characteristic (ROC) analysis demonstrated that high ANRIL expression [area under the ROC (auROC)= 0.755; 95% CI= 0.702-0.803] and low HOXA11-AS levels (auROC=0.712; 95% CI=0.657-0.763) predicted a high risk for ISR, and the combined score of ANRIL and HOXA11-AS (auROC= 0.844; 95% CI= 0.798-0.884) was more efficient at predicting ISR than either ANRIL or HOXA11-AS alone (P<0.001). In conclusion, increased ANRIL and decreased HOXA11-AS expressions were associated with ISR. However, combined ANRIL and HOXA11-AS plasma levels proved to be more effective at predicting ISR compared with either ANRIL or HOXA11-AS alone, suggesting that the multiplex detection of lncRNAs could be used to predict ISR in the future.

The Role of ANRIL in Atherosclerosis

“…High ANRIL expression was considered as an independent risk factor for in-stent restenosis. However, it was declared that the added diagnostic potential of ANRIL will be reached when combined with expression level of other lncRNAs like homeobox A11 antisense [ 115 ].…”

Spotlight on HOX cluster‑embedded antisense lncRNAs in cardiovascular diseases (Review)

“…Furthermore, another study indicated that the expression of HOTAIR is significantly downregulated with chronic HF ( 89 ). Finally, HOXA11-AS expression is downregulated in the plasma of patients with in-stent restenosis (ISR) compared to that in patients without ISR, and it was found to be an independent protective factor for ISR ( 90 ). In summary, the large amounts of data presented provide evidence for the use of HOX-lncRNAs as diagnostic markers of cardiovascular diseases, and future in-depth studies of these markers are expected to contribute to their use as potential therapeutic targets.…”