title: MicroRNA dysregulation in diabetic ischemic heart failure patients.
abstract: Increased morbidity and mortality associated with ischemic heart failure (HF) in type 2 diabetic patients requires a deeper understanding of the underpinning pathogenetic mechanisms. Given the implication of microRNAs (miRNAs) in HF, we investigated their regulation and potential role. miRNA expression profiles were measured in left ventricle biopsies from 10 diabetic HF (D-HF) and 19 nondiabetic HF (ND-HF) patients affected by non-end stage dilated ischemic cardiomyopathy. The HF groups were compared with each other and with 16 matched nondiabetic, non-HF control subjects. A total of 17 miRNAs were modulated in D-HF and/or ND-HF patients when compared with control subjects. miR-216a, strongly increased in both D-HF and ND-HF patients, negatively correlated with left ventricular ejection fraction. Six miRNAs were differently expressed when comparing D-HF and ND-HF patients: miR-34b, miR-34c, miR-199b, miR-210, miR-650, and miR-223. Bioinformatic analysis of their modulated targets showed the enrichment of cardiac dysfunctions and HF categories. Moreover, the hypoxia-inducible factor pathway was activated in the noninfarcted, vital myocardium of D-HF compared with ND-HF patients, indicating a dysregulation of the hypoxia response mechanisms. Accordingly, miR-199a, miR-199b, and miR-210 were modulated by hypoxia and high glucose in cardiomyocytes and endothelial cells cultured in vitro. In conclusion, these findings show a dysregulation of miRNAs in HF, shedding light on the specific disease mechanisms differentiating diabetic patients.
authors.affiliation: Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Greco
authors.forename: Pasquale
authors.initials: P
authors.lastname: Fasanaro
authors.forename: Serenella
authors.initials: S
authors.lastname: Castelvecchio
authors.forename: Yuri
authors.initials: Y
authors.lastname: D'Alessandra
authors.forename: Diego
authors.initials: D
authors.lastname: Arcelli
authors.forename: Marisa
authors.initials: M
authors.lastname: Di Donato
authors.forename: Alexis
authors.initials: A
authors.lastname: Malavazos
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Menicanti
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism
chemical_list: D035683:MicroRNAs