Dose-dependent effects of rosuvastatin on circulating microRNAs-27a and 221 levels in patients with coronary artery disease with type 2 diabetes mellitus

Abstract

Abstract Background Circulating microRNAs are capable of mediating cell-cell communication. MicroRNAs-27a and 221 serve an important regulatory role in both atherosclerosis and type 2 diabetes mellitus (T2DM). The lipid-lowering and pleiotropic effects of statins might be mediated by microRNAs. The purpose of the study was to investigate the dose-dependent effects of rosuvastatin on the circulating miRNAs-27a and 221 levels in patients with coronary artery disease (CAD) with T2DM. Methods The study included 22 patients with stable CAD with T2DM with rosuvastatin treatment at least 3 months (rosuvastatin 10 mg/day – 10 patients, rosuvastatin 20–40 mg/day – 12 patients), 16 patients with stable CAD with T2DM treated without statins. All patients received aspirin, beta-blockers, ACE inhibitors or sartans, metformin or its combination with sulfonylurea. The control group consisted of 16 healthy persons. MicroRNAs-27a-3p and 221-3p were determined in blood plasma by real time polymerase chain reaction. Small nuclear RNA U6 was used as endogenous control. Results expressed in relative units. Results In non-statin-treated patients with CAD with T2DM both microRNAs-27a (0,33 [0,15; 0,87]) and 221 (0,59 [0,27; 1,15]) levels were lower than in the control group ((0,90 [0,54; 2,62]), p=0,006 and (1,05 [0,57; 1,75]), p=0,043, respectively). In patients with CAD with T2DM treated with rosuvastatin 10 mg/day microRNA-27a level (0,44 [0,34; 0,69]) was decreased significantly in comparison with the control group (p=0,012) and was increased non-significantly in comparison non-statin-treated patients (p=0,439). In patients treated with rosuvastatin 20–40 mg/day microRNA-27a level (1,26 [0,31; 1,50]) was non-significantly higher than in the control group (p=0,559) and was significantly increased compared with non-statin-treated patients (p=0,038). MicroRNA-221 levels in patients treated both with rosuvastatin 10 mg/day (0,50 [0,28; 0,89]) and with rosuvastatin 20–40 mg/day (0,63 [0,40; 0,84]) were decreased in comparison with the control group (p=0,031 and p=0,042, respectively) and did not change significantly compared to patients treated without statins (p=0,928 and p=0,837, respectively). Conclusions In patients with CAD with T2DM circulating microRNAs-27a and -221 levels significantly decreased in comparison with control. Treatment with rosuvastatin in high doses (20–40 mg/day) but not in moderate dose (10 mg/day) was associated with the elevation of microRNA-27a level. Rosuvastatin at any doses did not influence on circulating microRNA-221 levels. These results revealed that rosuvastatin may serve protective roles in patients with CAD with T2DM by influencing on some microRNAs expression. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This research was funded by the Government as part of the research project to study the effects of circulating micro-ribonucleic acids in coronary artery disease with concomitant type 2 diabetes mellitus. This research did not receive any specific grant from funding.