MiR-144 protects the heart from hyperglycemia-induced injury by regulating mitochondrial biogenesis and cardiomyocyte apoptosis.
FASEB J
; 34(2): 2173-2197, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31907983
ABSTRACT
Several lines of evidence have revealed the potential of microRNAs (miRNAs, miRs) as biomarkers for detecting diabetic cardiomyopathy, although their functions in hyperglycemic cardiac dysfunction are still lacking. In this study, mitochondrial biogenesis was markedly impaired induced by high glucose (HG), as evidenced by dysregulated mitochondrial structure, reduced mitochondrial DNA contents, and biogenesis-related mRNA levels, accompanied by increased cell apoptosis. MiR-144 was identified to be decreased in HG-induced cardiomyocytes and in streptozotocin (STZ)-challenged heart samples. Forced miR-144 expression enhanced mitochondrial biogenesis and suppressed cell apoptosis, while miR-144 inhibition exhibited the opposite results. Rac-1 was identified as a target gene of miR-144. Decreased Rac-1 levels activated AMPK phosphorylation and PGC-1α deacetylation, leading to increased mitochondrial biogenesis and reduced cell apoptosis. Importantly, the systemic neutralization of miR-144 attenuated mitochondrial disorder and ventricular dysfunction following STZ treatment. Additionally, plasma miR-144 decreased markedly in diabetic patients with cardiac dysfunction. The receiver-operator characteristic curve showed that plasma miR-144 could specifically predict diabetic patients developing cardiac dysfunction. In conclusion, this study provides strong evidence suggesting that miR-144 protects heart from hyperglycemia-induced injury by improving mitochondrial biogenesis and decreasing cell apoptosis via targeting Rac-1. Forced miR-144 expression might, thus, be a protective strategy for treating hyperglycemia-induced cardiac dysfunction.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Miocitos Cardíacos
/
MicroARNs
/
Cardiomiopatías Diabéticas
/
Hiperglucemia
/
Mitocondrias Cardíacas
/
Miocardio
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China