title: Doxorubicin and Liposomal Doxorubicin Differentially Affect Expression of miR-208a and let-7g in Rat Ventricles and Atria.
abstract: Anthracyclines use is limited by profound cardiotoxicity. Involvement of miRNAs in anthracycline-induced cardiotoxicity (AIC) is still not completely understood. Thus, the expression of AIC-related microRNAs was determined in rat atria and ventricles after doxorubicin (DOX) and liposomal doxorubicin (L-DOX) administration. Vehiculum, DOX or L-DOX were applied intraperitoneally in a single dose to male Wistar rats (3 groups: control, DOX and L-DOX, respectively). Rats were sacrificed after 24 h, and samples from left atrium (LA)/ventricle (LV) and right atrium (RA)/ventricle (RV) were obtained. Expressions of miR-208a, let-7g and snU6 were determined using qRT-PCR. In the control group, miR-208a was highly abundant in the atria compared to the ventricles and in the left-sided structures compared to the right-sided structures, while let-7g showed only atrio-ventricular gradient with predominant expression in the atria. Administration of both DOX and L-DOX resulted in 38.87 and 23.57% reduction in miR-208a expression in the LV (p = 0.028) and in 13.79 and 14.70% reduction in let-7g expression in the LA (p = 0.015), respectively. Acute administration of DOX/L-DOX alters expression of miR-208a in LV and of let-7g in LA. These changes may partly contribute to the development of AIC.
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Building A20, 625 00, Brno, Czech Republic. jnmedved@seznam.cz.
authors.forename: Jan
authors.identifier: 0000-0001-5204-2067
authors.initials: J
authors.lastname: Novak
authors.affiliation: Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Sana
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Building A20, 625 00, Brno, Czech Republic.
authors.forename: Tibor
authors.initials: T
authors.lastname: Stracina
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Building A20, 625 00, Brno, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Novakova
authors.affiliation: Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015870:Gene Expression; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: C569395:MIRN208 microRNA, rat; C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Cardiotoxicity; Doxorubicin; let-7g; lipodox; miR-208a; microRNAs