title: Changes of microRNA-1, -15b and -21 levels in irradiated rat hearts after treatment with potentially radioprotective drugs.
abstract: The aim of this study was to measure expression levels of microRNAs (miRNAs) (miRNA-1, -15b and -21) in the rat myocardium after a single dose of ionizing radiation (6-7 Gy/min, total 25 Gy). The rats were treated with selected drugs (Atorvastatin, acetylsalicylic acid (ASA), Tadalafil, Enbrel) for six weeks after irradiation. MiRNAs levels were measured by RT-qPCR. Irradiation down-regulated miRNA-1 in irradiated hearts. In Tadalafil- and Atorvastatin-treated groups, miRNA-1 expression levels were further decreased compared with irradiated controls. However, Enbrel increased miRNA-1 level in irradiated hearts similarly to that in non-irradiated untreated group. Increase of miRNA-15b is pro-apoptotic in relationship with ischemia. Irradiation caused down-regulation of miRNA-15b. Administration of ASA in the irradiated group resulted in the increase of miRNA-15b expression compared to non-treated controls without irradiation. After Enbrel administration, miRNA-15b levels were overexpressed compared to non-treated normal group. MiRNA-21 belongs to the most markedly up-regulated miRNAs in response to cardiogenic stress. MiRNA-21 was increased nearly 2-fold compared to non-treated hearts whereas Tadalafil reduced miRNA-21 levels (about 40 %). Our study suggests that Enbrel and Tadalafil changed miRNAs expression values of the irradiated rats to the values of non-irradiated controls, thus they might be helpful in mitigation of radiation-induced toxicity.
authors.affiliation: Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia. branislav.kura@savba.sk.
authors.forename: B
authors.initials: B
authors.lastname: Kura
authors.forename: C
authors.initials: C
authors.lastname: Yin
authors.forename: K
authors.initials: K
authors.lastname: Frimmel
authors.forename: J
authors.initials: J
authors.lastname: Krizak
authors.forename: L
authors.initials: L
authors.lastname: Okruhlicova
authors.forename: R C
authors.initials: RC
authors.lastname: Kukreja
authors.forename: J
authors.initials: J
authors.lastname: Slezak
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D006321:Heart / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D017208:Rats, Wistar
chemical_list: D035683:MicroRNAs; D011837:Radiation-Protective Agents