title: Serum microRNA-1 and microRNA-133a levels reflect myocardial steatosis in uncomplicated type 2 diabetes.
abstract: Using in vitro, in vivo and patient-based approaches, we investigated the potential of circulating microRNAs (miRNAs) as surrogate biomarkers of myocardial steatosis, a hallmark of diabetic cardiomyopathy. We analysed the cardiomyocyte-enriched miRNA signature in serum from patients with well-controlled type 2 diabetes and with verified absence of structural heart disease or inducible ischemia, and control volunteers of the same age range and BMI (N = 86), in serum from a high-fat diet-fed murine model, and in exosomes from lipid-loaded HL-1 cardiomyocytes. Circulating miR-1 and miR-133a levels were robustly associated with myocardial steatosis in type 2 diabetes patients, independently of confounding factors in both linear and logistic regression analyses (P < 0.050 for all models). Similar to myocardial steatosis, miR-133a levels were increased in type 2 diabetes patients as compared with healthy subjects (P < 0.050). Circulating miR-1 and miR-133a levels were significantly elevated in high-fat diet-fed mice (P < 0.050), which showed higher myocardial steatosis, as compared with control animals. miR-1 and miR-133a levels were higher in exosomes released from lipid-loaded HL-1 cardiomyocytes (P < 0.050). Circulating miR-1 and miR-133a are independent predictors of myocardial steatosis. Our results highlight the value of circulating miRNAs as diagnostic tools for subclinical diabetic cardiomyopathy.
authors.affiliation: Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. DGonzalo@santpau.cat.|CIBERCV, Institute of Health Carlos III, Madrid, Spain. DGonzalo@santpau.cat.
authors.forename: D
authors.initials: D
authors.lastname: de Gonzalo-Calvo
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: R W
authors.initials: RW
authors.lastname: van der Meer
authors.affiliation: Department of Medicine, Kantonsspital Baden AG, Baden, Switzerland.
authors.forename: L J
authors.initials: LJ
authors.lastname: Rijzewijk
authors.affiliation: Department of Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: J W A
authors.initials: JW
authors.lastname: Smit
authors.affiliation: Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.|CIBERCV, Institute of Health Carlos III, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Revuelta-Lopez
authors.affiliation: Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.|CIBERCV, Institute of Health Carlos III, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Nasarre
authors.affiliation: IIB Sant Pau, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona-CIBER de Diabetes y Enfermedades Metabolicas Asociadas, Barcelona, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: Escola-Gil
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lamb
authors.affiliation: Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. CLlorente@santpau.cat.|CIBERCV, Institute of Health Carlos III, Madrid, Spain. CLlorente@santpau.cat.|Biomedical Research Institute of Barcelona, CSIC, Barcelona, Spain. CLlorente@santpau.cat.
authors.forename: V
authors.initials: V
authors.lastname: Llorente-Cortes
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D058065:Diabetic Cardiomyopathies / Q000097:blood* / Q000209:etiology; D059305:Diet, High-Fat; D055354:Exosomes; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D015415:Biomarkers; C544547:MIRN1 microRNA, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs