Plasma MicroRNAs as Potential Noninvasive Biomarkers for In-Stent Restenosis

Abstract

ObjectiveTo investigate whether microRNAs (miRs) can serve as novel biomarkers for in-stent restenosis (ISR).MethodsThis retrospective, observational single-centre study was conducted at the cardiovascular department of a tertiary hospital centre in the north of China. Follow-up coronary angiography at 6 to 12 months was performed in 181 consecutive patients implanted with drug-eluting stents. Fifty-two healthy volunteers served as the control group. The plasma miRs levels were analyzed by quantitative real-time PCR. Receiver-operating characteristic curve (ROC) analysis was performed to investigate the characters of these miRs as potential biomarkers of ISR.ResultsMiR-21 levels in ISR patients were significantly higher than those in non-ISR patients and healthy controls (P<0.05), while miR-100 (P<0.05), miR-143 (P<0.001) and miR-145 (P<0.0001) levels were significantly decreased in ISR patients. Further analysis showed that miR-21 levels were remarkably increased (P = 0.045), while miR-100 (P = 0.041), miR-143 (P = 0.029) and miR-145 (P<0.01) levels were dramatically decreased in patients with diffuse ISR compared to those with focal ISR. ROC analysis demonstrated that the area under curve of miR-145, miR-143, miR-100 and miR-21 were 0.880 (95% confidence interval; CI = 0.791–0.987, P<0.001), 0.818 (95% confidence interval; CI = 0.755–0.963, P<0.001), 0.608 (95% confidence interval; CI = 0.372–0.757, P<0.05) and 0.568 (95% confidence interval; CI = 0.372–0.757, P<0.05), with specificity of 83.1%, 80.1%, 68.9% and 68.6%, and sensitivity of 88.7%, 82.1%, 60.2% and 50.1%, respectively.ConclusionsCirculating miR-143 and miR-145 levels are associated with the occurrence of ISR and can serve as novel noninvasive biomarkers for ISR.

miR-21 is associated with fibrosis and right ventricular failure

“…*P < 0.01, **P < 0.001. er candidate. miR-21 has been previously described as a biomarker for atherosclerosis and heart transplant rejection and in multiple cancers (22,24,25,45,46). We found that plasma miR-21 increased early during the stage of diastolic dysfunction and positively correlated with the degree of tissue fibrosis.…”

“…Circulating miRs in body fluids have been described as biomarkers of cardiovascular disease and cancer progression (21)(22)(23). We therefore evaluated the expression of the upregulated RV profibrotic miRs in plasma to evaluate their usefulness as potential biomarkers of fibrosis in the RV.…”

microRNAs in cardiovascular disease – clinical application

“…Molecular aspects gave rise to analyses investigating miRNAs as biomarkers for in-stent restenosis [40,[112][113][114]. Indeed, circulating miR-21, miR-143, miR-145, and miR-100 were reported to be dysregulated in ISR patients compared with control patients without ISR after drug eluting stent implantation [115]. A recent study confirmed dysregulated circulating miR-21 levels in pig and mouse models after coronary stenting [116].…”

Role of noncoding RNA in vascular remodelling

“…These signalling pathways are central mediators of the vascular remodelling process following acute injury, regulating VSMC proliferation, migration, and phenotype [35]. Similar to the Ji et al study described above, upregulation of miR-21 has been observed across many in vivo models of vascular injury, including mouse and pig models of vein graft failure, and mouse models of ISR [29] showed that miR-21 could act as a potential biomarker for the development of ISR [39]. In PAH, manipulation of miR-21 levels has also been shown to affect the vascular remodelling that leads to the formation of obstructive lesions in the pulmonary vasculature.…”