Serum miRNA Profile in Diabetic Patients With Ischemic Heart Disease as a Promising Non-Invasive Biomarker

Abstract

The increasing morbidity and mortality of type 2 diabetic mellitus (T2DM) patients with ischemic heart disease (IHD) highlight an urgent need to identify early biomarkers, which would help to predict individual risk of development of IHD. Here, we postulate that circulating serum-derived micro RNAs (miRNAs) may serve as potential biomarkers for early IHD diagnosis and support the identification of diabetic individuals with a predisposition to undergo IHD. We obtained serum samples from T2DM patients either with IHD or IHD-free and analysed the expression levels of 798 miRNAs using the NanoString nCounter technology platform. The prediction of the putative miRNAs targets was performed using the Ingenuity Pathway Analysis (IPA) software. Gene Ontology (GO) analysis was used to identify the biological function and signalling pathways associated with miRNA target genes. Hub genes of protein-protein interaction (PPI) network were identified by STRING database and Cytotoscape tool. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of identified miRNAs. Real-time quantitative polymerase chain reaction (qRT-PCR) was used for nCounter platform data validation. Our data showed that six miRNAs (miR-615-3p, miR-3147, miR-1224-5p, miR-5196-3p, miR-6732-3p, and miR-548b-3p) were significantly upregulated in T2DM IHD patients compared to T2DM patients without IHD. Further analysis indicated that 489 putative target genes mainly affected the endothelin-1 signalling pathway, glucocorticoid biosynthesis, and apelin cardiomyocyte signalling pathway. All tested miRNAs showed high diagnostic value (AUC = 0.779 - 0.877). Taken together, our research suggests that circulating miRNAs might have a crucial role in the development of IHD in diabetic patients and may be used as a potential biomarker for early diagnosis.

Anthocyanin-rich extract from black beans exerts anti-diabetic effects in rats through a multi-genomic mode of action in adipose tissue

“…Similarly, it has been demonstrated that miR-615 is expressed in adipose tissue in humans and that its expression changes with the obesity ( 66 ). Moreover, the expression of this miRNA has also been identified in patients with diabetes ( 67 ). Together with miRNAs, our analysis also revealed changes in the expression of long non-coding RNAs.…”

Empagliflozin Improves the MicroRNA Signature of Endothelial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Diabetes

“…We have recently demonstrated that empagliflozin significantly improves cognitive impairment in frail older diabetics with HFpEF (Mone et al, 2022c), showing also a correlation between physical and cognitive impairment (Mone et al, 2022a). MicroRNAs (miRs) are small non-coding RNAs molecules of 18-24 nucleotides, which typically repress messenger RNAs (mRNAs) by binding their 3′ untranslated region (Santulli, 2015;Fridrichova and Zmetakova, 2019;Stavast and Erkeland, 2019;Hu et al, 2021;Mirzaei et al, 2021;Mone et al, 2021b;Bielska et al, 2022;Karagiannopoulos et al, 2022;Mauro et al, 2022;Moisoiu et al, 2022;Qiu et al, 2022;Traber and Yu, 2022;Yaylim et al, 2022;Zeng et al, 2022). Substantial evidence has shown that miRs exert their activity in many biological processes and several miRs have been proposed as biomarkers and potential targets of novel therapeutic strategies (Creemers et al, 2012;Wronska et al, 2015;Barwari et al, 2016;Zarone et al, 2017;Chen et al, 2018;Wong et al, 2018;Morelli et al, 2019;Kawasaki et al, 2020;Wang et al, 2020;Fonseca et al, 2021;Gambardella et al, 2021;Bonnet et al, 2022;Gambardella et al, 2022a;Gambardella et al, 2022b;Kansakar et al, 2022;Varzideh et al, 2022).…”