miR-21-5p as a potential biomarker of inflammatory infiltration in the heart upon acute drug-induced cardiac injury in rats.
Toxicol Lett
; 286: 31-38, 2018 Apr.
Article
en En
| MEDLINE
| ID: mdl-29355689
Investigation of genomic changes in cardiotoxicity can provide novel biomarkers and insights into molecular mechanisms of drug-induced cardiac injury (DICI). The main objective of this study was to identify and characterize dysregulated microRNAs (miRNAs) in the heart associated with cardiotoxicity. Wistar rats were dosed once with either isoproterenol (1.5â¯mg/kg, i.p), allylamine (100â¯mg/kg, p.o.) or the respective vehicle controls. Heart tissue was collected at 24â¯h, 48â¯h and 72â¯h post-drug administration and used for histopathological assessment, miRNA profiling, immunohistochemical analysis and in situ hybridization. Multiplex analysis of 68 miRNAs in the heart revealed a significant upregulation of several miRNAs (miR-19a-3p, miR-142-3p, miR-155-5p, miR-208b-3p, miR-21-5p) after isoproterenol and one miRNA (miR-21-5p) after allylamine administration. Localization of miR-21-5p was specific to inflammatory cell infiltrates in the heart after both treatments. Immunohistochemical analysis of Stat3, a known miR-21-5p regulator, also confirmed its upregulation in cardiomyocytes and inflammatory cell infiltrates. The toxicity signatures based on miRNA networks, identified in vivo, can potentially be used as mechanistic biomarkers as well as to study cardiotoxicity in vitro in order to develop sensitive tools for early hazard identification and risk assessment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Cardiopatías
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Inflamación
/
Miocardio
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Toxicol Lett
Año:
2018
Tipo del documento:
Article
País de afiliación:
Bélgica
Pais de publicación:
Países Bajos