Expression of angiogenic MicroRNAs in endothelial progenitor cells from type 1 diabetic patients with and without diabetic retinopathy

Abstract

Purpose. MicroRNA (miR) expression in endothelial progenitor cells (EPCs) in type 1 diabetes (DM1) and its relation with different stages of diabetic retinopathy (DR) have not been reported to date. Our aim was to analyze miR-222, miR-221, and miR-126 expression in EPCs from DM1 patients with and without DR. Methods. We included 41 patients with DR, 35 without DR, and 38 controls. Blood was collected for flow cytometry and EPC culture. Total RNA was extracted and purified and real-time quantitative PCR was performed for miR expression in cultured EPCs. Relative changes in miR expression were analyzed with the 2 −ΔΔC T method. Results. Circulating EPCs were reduced and miR-126 expression was increased in DM1 compared to controls (0.030 [interquartile range [IQR], 0.020–0.050] vs. 0.060 [IQR, 0.030–0.110], P = 0.004; 1.740 [IQR, 0.890–4.120] vs. 0.990 [IQR, 0.487–3.015], P = 0.047 respectively) without differences between patients with and without DR. Patients with DR had higher expression of miR-221 than those without DR (1.405 [IQR, 0.820–2.867] vs. 0.915 [IQR, 0.507–1.292], P = 0.019) without differences among degrees of DR. Circulating EPCs were reduced in patients on statins (0.010 [IQR, 0.010–0.050] vs. 0.045 [IQR, 0.020–0.087], P = 0.008), and miR-221 expression increased in patients on angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blocker (ARB) II (1.430 [IQR, 1.160–2.705] vs. 1.000 [IQR, 0.520–1.330], P = 0.021) compared to those without treatment. MicroRNA-126 expression was associated with body mass index (BMI; ρ = −0.267, P = 0.026) and diastolic blood pressure (ρ = −0.267, P = 0.034). MicroRNA-221 was associated with triglyceride concentration (ρ = 0.296, P = 0.012). Conclusions. Circulating EPCs were reduced and miR-126 expression was increased in DM1 compared to controls. Patients with DR had higher expression of miR-221 than those without DR. The identification of biomarkers of diabetic complications might be useful for monitoring disease progression and potential therapeutic targets.