Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA-21 expression, Akt and the Bcl-2/Bax pathway

Autor: Jingyun Bai, Donghai Liu, Xin Zhang, Chenhui Qiao, Weihua Zhang, Ning Ma, Hong Luo
Rok vydání: 2016
Předmět:
0301 basic medicine
Cardiac function curve
Cancer Research
Pathology
medicine.medical_specialty
cardiac ischemia/reperfusion injury
trimetazidine
Myocardial Infarction
Trimetazidine
Apoptosis
Myocardial Reperfusion Injury
Pharmacology
Biochemistry
03 medical and health sciences
0302 clinical medicine
Bcl-2-associated X protein
Genetics
medicine
Animals
Humans
Myocardial infarction
Molecular Biology
Protein kinase B
bcl-2-Associated X Protein
Gene knockdown
biology
Myocardium
Akt
Articles
medicine.disease
Rats
Oncogene Protein v-akt
Disease Models
Animal
MicroRNAs
030104 developmental biology
Gene Expression Regulation
Proto-Oncogene Proteins c-bcl-2
Oncology
030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
Reperfusion injury
Signal Transduction
microRNA-21
Bcl-2/Bax
medicine.drug
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
Popis: Trimetazidine is a piperazine-derived metabolic agent, which exerts cell protective effects and has been reported to be efficient in the treatment of chronic stable angina pectoris. In addition, it has been shown to exert protection against acute myocardial infarction. The present study aimed to investigate whether trimetazidine protects against cardiac ischemia/reperfusion (I/R) injury, and to determine whether its curative effects are associated with microRNA (miRNA)-21 expression, Akt, and the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) pathway. Cardiac I/R injury was induced by ligating the left anterior descending coronary artery in adult rats. Subsequently, cardiac function was evaluated, and the expression levels of miRNA-21, Bcl-2, Bax and phosphorylated-Akt were detected using quantitative polymerase chain reaction and western blotting. The results indicated that trimetazidine was able to significantly protect cardiac function and reduce infarct size in rats following cardiac I/R injury. Furthermore, trimetazidine significantly promoted miRNA-21 expression and phosphorylated-Akt protein expression, and reduced the Bcl-2/Bax ratio in rats following cardiac I/R injury. Knockdown of miRNA-21 using anti-miR-21 plasmids was able to reverse the protective effects of trimetazidine against cardiac I/R injury. These results indicated that miRNA-21 serves a protective role in cardiac I/R injury via Akt and the Bcl-2/Bax pathway. In addition, trimetazidine exerts protective effects against cardiac I/R injury through cardiac miRNA-21 expression, Akt, and the Bcl-2/Bax pathway. Therefore, the present study provided evidence regarding the protective effects of miRNA-21 on cardiac I/R injury following treatment with trimetazidine in vivo.
Databáze: OpenAIRE
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