title: Expression of Angiogenic MicroRNAs in Endothelial Progenitor Cells From Type 1 Diabetic Patients With and Without Diabetic Retinopathy.
abstract: OBJECTIVE
  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-ΔΔCT 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.
authors.affiliation: Department of Endocrinology Diabetes and Nutrition, Instituto de Investigación Sanitaria San Carlos (IdISSC) Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: García de la Torre
authors.affiliation: Research Unit, Department of Internal Medicine, IdISSC, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Fernández-Durango
authors.affiliation: Department of Endocrinology Diabetes and Nutrition, Instituto de Investigación Sanitaria San Carlos (IdISSC) Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Gómez
authors.affiliation: Department of Preventive Medicine, IdISSC, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Fuentes
authors.affiliation: Department of Ophthalmology, IdISSC, Complutense University and Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: Manuela
authors.initials: M
authors.lastname: Roldán-Pallarés
authors.affiliation: Department of Ophthalmology, IdISSC, Complutense University and Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Donate
authors.affiliation: Department of Endocrinology Diabetes and Nutrition, Instituto de Investigación Sanitaria San Carlos (IdISSC) Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Barabash
authors.affiliation: Department of Endocrinology Diabetes and Nutrition, Instituto de Investigación Sanitaria San Carlos (IdISSC) Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Alonso
authors.affiliation: Department of Endocrinology Diabetes and Nutrition, Instituto de Investigación Sanitaria San Carlos (IdISSC) Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Runkle
authors.affiliation: Department of Endocrinology Diabetes and Nutrition, Instituto de Investigación Sanitaria San Carlos (IdISSC) Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Durán
authors.affiliation: Department of Endocrinology Diabetes and Nutrition, Instituto de Investigación Sanitaria San Carlos (IdISSC) Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Rubio
authors.affiliation: Department of Endocrinology Diabetes and Nutrition, Instituto de Investigación Sanitaria San Carlos (IdISSC) Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Alfonso L
authors.initials: AL
authors.lastname: Calle-Pascual
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; C527111:MIRN126 microRNA, human; C525709:MIR221, human; C525710:MIR222, human