Plasma circulating microRNAs in patients with stable coronary artery disease - impact of different cardiovascular risk profiles and glomerular filtration rates

Abstract

Mērķis: plazmā cirkulējošā mikroRNS -126, -145 un -155 ir saistītas ar asinsvadu remodelāciju, aterosklerozes bojājumu veidošanos un pangas nestabilitāti. Šajā pētījumā tika novērtēts plazmā cirkulējošo mikroRNS līmeņi pacientiem ar stabilu koronāro artēriju slimību (KAS), dažādi kardiovaskulārā riska profili un dažādi glomerulārās filtrācijas ātrumi (GFĀ). Metodes un rezultāti: pētījumā tika iekļauti četrdesmit pacienti ar stabilu KAS plānveida perkutānai koronārajai intervencei (PKI). Pirms PKI tika ņemti tukšā dūšā asins paraugi, lai novērtētu klīniskos parametrus un miRNS-126 un miRNS-155 daudzumu. GFĀ tika aprēķināts pēc MDRD un CKD-EPI formulām, un tika aprēķināts KAS smagums saskaņā ar SYNTAX skalas punktiem. Visi šie parametri tika korelēti ar mikroRNS. MikroRNS-126 ekspresija pozitīvi korelēja ar augstāku SINTAX rādītāju (r = 0,337; p = 0,034); tomēr netika novērotas korelācijas starp mikroRNS-126, GFĀ un klīniskajām parametriem. Savukārt, mikroRNS-155 korelēja ar paaugstinātu triglicerīdu līmeni (r = 0,317; P = 0,049), C-peptīdu (r = 0,452; P = 0,011), un HOMA indeksu(r = 0,447; P = 0,012) un augstāku ķermeņa masas indeksu (ĶMI) (r = 0,385; P = 0,015). GFĀ un mikroRNS-155 (MDRD – Rho=0,353; P = 0,027. CKD-EPI – Rho=0,357; P = 0,026) tika konstatēta mērena korelācija, lai gan mikroRNS-155 nebija korelācija ar SYNTAX punktu skaitu. Secinājums: plazmā cirkulējošā mikroRNS-126 līmenis bija paaugstināts pacientiem ar smagu aterosklerozi, ko nosaka SYNTAX rādītājs. Tika novērota paaugstināta mikroRNS-155 ekspresija pacientiem ar 1. stadijas GFĀ, bet bija zemāks pacientiem ar 2. un 3. stadijas GFĀ. Plazmā cirkulējošajam mikroRNS-155 bija pozitīva korelācija ar augstāku ĶMI, HOMA indeksu, C-peptīdu un triglicerīdiem. Lai gan ir nepieciešami turpmāki pētījumi, lai apstiprinātu mikroRNS-155 un mikroRNS-126 lomu diagnostikā. Tie jau šobrīd var kalpot kā potenciālie biomarķieri, kas nosaka KAS smagumu, samazinātu nieru darbība un metabolisko sindromu.Background and Aim: Plasma circulating microRNA (miRNA)-126, -145, and -155 are associated with vascular remodeling, atherosclerotic lesion formation, and plaque vulnerability. In this study, we evaluated the levels of plasma circulating miRNAs in patients with stable coronary artery disease (CAD), different cardiovascular risk profiles, and different glomerular filtration rates (GFR). Methods and Results: Forty patients with stable CAD admitted for elective percutaneous coronary intervention (PCI) were enrolled in a prospective study. Before PCI, fasting blood samples were obtained to evaluate clinical parameters and miRNA-126 and miRNA-155 expression. The GFR was calculated by the MDRD and CKD-EPI formulas, and the severity of CAD was calculated according to the SYNTAX score. All these parameters were correlated with miRNAs. The association between miRNA levels and clinical characteristics was evaluated. The expression of miRNA-126 positively correlated with a higher SYNTAX score (r = 0.337; p=0.034); however, no significant correlations between miR-126, GFR, and clinical characteristics were observed. Higher plasma levels of miRNA-155 correlated with increased levels of triglycerides (r = 0.317; P = 0.049), C-peptide (r = 0.452; P = 0.011), and the HOMA index (r = 0.447; P = 0.012) and a higher body mass index (BMI) (r = 0.385; P = 0.015). GFR and miRNA-155 (MDRD – Rho=0.353; P = 0.027. CKD-EPI – Rho=0.357; P = 0.026) were found to have a moderate correlation, although miRNA-155 had no correlation with the SYNTAX score. Conclusion: Plasma circulating miRNA-126 levels were increased in patients with severe atherosclerosis as determined by the SYNTAX score. Elevated miRNA-155 expression was observed in patients with Stage 1 GFR but was lower in patients with Stages 2 and 3 GFR. Plasma circulating miRNA-155 had positive correlations with higher levels of BMI, HOMA index, C-peptide, and triglycerides. Relevance for Patients: Although further investigations are needed to confirm the role of miRNA-155 and miRNA-126, they may serve as potential biomarkers detecting severity of CAD, lowering of kidney function and metabolic syndrome.