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Published on: July 14, 2016
Inhibitory effect of atorvastatin on AGE-induced HCAEC apoptosis by upregulating HSF-1 protein
1Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China. yingcnli@163.com
Insights
Advanced Glycation End-products (AGEs) increase human coronary artery endothelial cell (HCAEC) apoptosis via the PI3K/AKT pathway. Atorvastatin may reduce this apoptosis by upregulating HSF-1.
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Function
- Pharmacology
Background:
- Advanced Glycation End-products (AGEs) are implicated in endothelial dysfunction.
- Endothelial cell apoptosis contributes to cardiovascular disease pathogenesis.
- Atorvastatin is a statin drug with potential pleiotropic effects beyond lipid lowering.
Purpose of the Study:
- To investigate the effect of atorvastatin on AGEs-induced apoptosis in human coronary artery endothelial cells (HCAEC).
- To elucidate the underlying molecular mechanisms involving the PI3K/AKT pathway and heat shock factors.
Main Methods:
- HCAEC were treated with varying concentrations of AGEs.
- The effects of atorvastatin and a PI3K inhibitor on cell apoptosis were assessed.
- Levels of PI3K, P-Akt, HSF-1, and HSP-70 mRNA were measured.
Main Results:
- AGEs increased HCAEC apoptosis in a dose-dependent manner.
- Atorvastatin reduced AGEs-induced apoptosis, an effect blunted by PI3K inhibition.
- AGEs decreased HSF-1 and HSP-70 mRNA expression, while atorvastatin partially restored it, also sensitive to PI3K inhibition.
Conclusions:
- AGEs promote HCAEC apoptosis through the PI3K/AKT pathway.
- Atorvastatin may mitigate AGEs-induced endothelial apoptosis, potentially via HSF-1 modulation.
- The PI3K/AKT pathway is crucial in mediating the protective effects of atorvastatin against AGEs toxicity.
Abstract:
This study evaluates effect and mechanism of atorvastatin on human coronary artery endothelial cells (HCAEC) apoptosis. Results have shown that HCAEC apoptosis had increased with increasing concentration of AGEs. Atorvastatin may decrease HCAEC apoptosis, but the effect can be attenuated by PI3K inhibitor. Secretion of PI3K and P-Akt in HCAEC increased with increasing concentration of AGEs. Secretion of PI3K in HCAEC may be decreased by atorvastatin. The effect may be attenuated by PI3K inhibitor. HSF-1, HSP-70 mRNA expression level decreased with increasing concentration of AGEs. Atorvastatin may attenuate AGEs-induced HSF-1, HSP-70 mRNA expression in HCAEC, but the effect can be attenuated by PI3K inhibitor. It can be concluded that AGE can dose-dependently promote HCAEC apoptosis by the PI3K/AKT pathway. Atorvastatin may attenuate the effect possibly by upregulating HSF-1.
