The role of circulating miRNAs as predictive biomarkers for the neointimal hyperplasia after femoro-popliteal endovascular procedures for symptomatic peripheral arterial disease

BACKGROUND: The neointimal hyperplasia (NIH) is the main cause of the early failure of a vascular revascularization either by open or endovascular procedure. Currently, there are not available biomarkers which can predict the NIH onset. The aim of the present study was to investigate on the quantitative and qualitative changes of circulating miRNAs after endovascular procedures at the arteries of the lower extremities in patients suffering from symptomatic peripheral arterial disease (PAD) in order to hypothesize a possible their implication as predictors of the onset of NIH. METHODS: This is an observational and prospective study conducted in patients suffering from symptomatic PAD and deemed as candidate for a femoro-popliteal endovascular revascularization. We selected 18 miRNAs as candidates for the quantitative assessment. Blood samples were obtained six hours before surgery and after the revascularization at 12 hours, 48 hours and at 14 days. The extraction of RNA was performed on the exosomes (Norgen's Plasma/Serum Exosome Purification and RNA Isolation Maxi Kit). The RNA retrostrascription obtained from exosomes was quantified using the Real time PCR (qPCR) of the miRNA selected. Follow-up consisted of clinical and ultrasound examination in outpatients at one month, three months and annually thereafter. Restenosis was defined as lumen narrowing at least of 50% or an increase of the peak systolic flow at Duplex examination at least 1.6 m/s. RESULTS : From April 2021 to April 2022 were included 10 patients. They were mainly men and suffered from critical limb threatening ischemia. Most of the patients were affected by systemic hypertension and diabetes. Two patients developed hemodynamic restenosis at three months and another developed non-hemodynamic restenosis less than 50% at 12 months. After the revascularization miRNAs showed three different behaviors. One group (miRNA-21, 146, 92a, 126,221/222) showed an upregulation, the second group (miRNA-424, 145,195,100) downregulation and the last one (miRNA-22, 125a, 217, 143) presented no changes. Another characteristic consisted about the time-window after the procedure where a miRNA was subject to quantitative changes, resulting different for specific miRNA. CONCLUSIONS: The quantitative changes of miRNAs after a femoro-popliteal endovascular procedure occur in specific intervals which result to be different for a specific miRNA. The detection of these changes in their specific intervals assumes a more accurate predictive value for the NIH onset. In case of considering a miRNA as a potential target, the treatment would result more efficient considering its own temporal window.