MiR-21-5p and miR-126a-3p levels in plasma and circulating angiogenic cells: relationship with type 2 diabetes complications

Abstract

// Fabiola Olivieri 1,2 , Liana Spazzafumo 3 , Massimiliano Bonafè 4 , Rina Recchioni 2 , Francesco Prattichizzo 1 , Fiorella Marcheselli 2 , Luigina Micolucci 1 , Emanuela Mensà 2 , Angelica Giuliani 1 , Gabriele Santini 1 , Mirko Gobbi 1 , Raffaella Lazzarini 2 , Massimo Boemi 5 , Roberto Testa 6 , Roberto Antonicelli 7 , Antonio Domenico Procopio 1,2 and Anna Rita Bonfigli 8 1 Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy 2 Center of Clinical Pathology and Innovative Therapy, INRCA-IRCCS National Institute , Ancona, Italy 3 Center of Biostatistics, INRCA-IRCCS National Institute, Ancona, Italy 4 Department of Experimental, Diagnostic and Specialty Medicine, DIMES, University of Bologna, Bologna, Italy 5 Metabolic Diseases and Diabetology Unit, INRCA-IRCCS National Institute, Ancona, Italy 6 Experimental Models in Clinical Pathology, INRCA-IRCCS National Institute, Ancona, Italy 7 UTIC-Cardiology Unit, INRCA-IRCCS National Institute, Ancona, Italy 8 Scientific Direction, INRCA-IRCCS, National Institute, Ancona, Italy Correspondence to: Fabiola Olivieri, email: // Keywords : miR-21, miR-126, type 2 diabetes, diabetes complication, circulating miRNAs, Gerotarget Received : September 10, 2015 Accepted : October 02, 2015 Published : October 19, 2015 Abstract Innovative biomarkers are required to manage type 2 diabetic patients (T2DM). We focused our study on miR-126-3p and miR-21-5p levels, as biomarkers of endothelial function and inflammation. MiRNAs levels were measured in plasma from 107 healthy subjects (CTR) and 193 diabetic patients (T2DM), 76 without (T2DM NC) and 117 with (T2DM C) complications. When diabetic complication were analysed as a whole, miR-126-3p and miR-21-5p levels declined significantly from CTR to T2DM NC and T2DM C patients. When miRNAs levels were related to specific complications, significantly higher miR-21-5p levels (0.46 ± 0.44 vs. 0.26±0.33, p < 0.001) and significant lower miR-126-3p levels (0.21±0.21 vs . 0.28±0.22, p = 0.032) were found in T2DM with previous major cardiovascular events (MACE) vs. all the others T2DM patients. To confirm these results we focused on circulating angiogenic cells (CACs) from a subgroup of 10 CTR, 15 T2DM NC and 15 T2DM patients with MACE. CACs from T2DM patients expressed higher miR-21-5p and lower miR-126-3p levels than CACs from CTR. Furthermore, CACs from T2DM + MACE showed the highest levels of miR-21-5p. Circulating miR-21-5p and miR-126-3p emerge as dynamic biomarkers of systemic inflammatory/angiogenic status. Their expression levels in CACs from T2DM with MACE suggest a shift from a proangiogenic to a proinflammatory profile.