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Atorvastatin protects cardiomyocytes against OGD/R‑induced apoptosis by inhibiting miR‑199a‑5p
Yong Li1, Ting Jiang2, Xingli Fu3
1Department of Cardiology, The Affiliated Wujin Hospital of Jiangsu University, Changzhou, Jiangsu 213017, P.R. China.
Abstract:
The present study aimed to evaluate the protective effects of atorvastatin against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its underlying mechanisms. The direct cytotoxic effects of oxygen‑glucose deprivation/reperfusion (OGD/R) on cardiomyocytes with and without atorvastatin pretreatment were evaluated. The effects of atorvastatin on the expression of glycogen synthase kinase‑3β (GSK‑3β) and microRNA (miR)‑199a‑5p were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses. In addition, the expression levels of GSK‑3β in cells with miR‑199a‑5p upregulation and downregulation were detected using RT‑qPCR, western blot and immunohistochemical analyses. Pretreatment with atorvastatin significantly improved the recovery of cell viability from OGD/R (P<0.05). In addition, atorvastatin pretreatment significantly increased the expression of GSK‑3β at the mRNA and protein levels, and the expression of miR‑199a‑5p at the mRNA level (all P<0.05). The upregulation and downregulation of miR‑199a‑5p respectively decreased and increased the expression of GSK‑3β at the mRNA and protein levels. These results suggested that atorvastatin provided cardioprotective effects against I/R injury via increasing the expression of GSK‑3β through the inhibition of miR‑199a‑5p.
Insights
Atorvastatin protects heart cells from injury by increasing glycogen synthase kinase-3β (GSK-3β) expression. This occurs through inhibiting microRNA-199a-5p, offering a potential therapeutic strategy for myocardial ischemia/reperfusion injury.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Myocardial ischemia/reperfusion (I/R) injury poses a significant clinical challenge.
- Cardiomyocyte protection strategies are crucial for managing heart conditions.
- Understanding the molecular mechanisms of drug-induced cardioprotection is essential.
Purpose of the Study:
- To evaluate the cardioprotective effects of atorvastatin against I/R injury in cardiomyocytes.
- To elucidate the underlying molecular mechanisms involving GSK-3β and miR-199a-5p.
- To assess the direct cytotoxic effects of oxygen-glucose deprivation/reperfusion (OGD/R) on cardiomyocytes.
Main Methods:
- Utilized oxygen-glucose deprivation/reperfusion (OGD/R) model in cardiomyocytes.
- Assessed atorvastatin's effects on cell viability.
- Quantified gene and protein expression of GSK-3β and miR-199a-5p using RT-qPCR, western blot, and immunohistochemistry.
Main Results:
- Atorvastatin pretreatment significantly improved cardiomyocyte viability after OGD/R.
- Atorvastatin increased both mRNA and protein levels of GSK-3β.
- Atorvastatin upregulated miR-199a-5p expression, which in turn modulated GSK-3β levels.
Conclusions:
- Atorvastatin exhibits protective effects against I/R injury in cardiomyocytes.
- The mechanism involves atorvastatin increasing GSK-3β expression.
- This increase is mediated by the inhibition of miR-199a-5p, highlighting a novel therapeutic pathway.