Abstract
This study was designed to investigate the apoptosis induced by oxidized low-density lipoprotein (ox-LDL) in cultured neonatal rat cardiomyocytes and explore the possible mechanisms. We evaluated whether ox-LDL-induced apoptosis depended in part on the activation of toll-like receptor-4(TLR4)/Nuclear factor κB (NF-κB) signaling pathway. Cells were cultivated with and without ox-LDL. Cell apoptosis was evaluated by flow cytometry. Immunofluorescence, western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to assess protein or mRNA expressions. Resatorvid (TAK-242), an exogenous synthetic antagonist for TLR4, was used to inhibit TLR4 signal transduction. Dose- and time-dependent apoptotic index of cardiomyocytes occurred after ox-LDL treatment. Incubation of cardiomyocytes with ox-LDL (50 μg/mL) for 24 hours increased TLR4 and NF-κB expressions significantly. Decrease of Bcl-2/Bax protein ratio, activation of caspase-3 and 9 were also detected. Ox-LDL-induced cardiomyocyte apoptosis, TLR4 and NF-κB expressions were attenuated by pretreatment with TAK-242. In conclusion, our findings indicate that the apoptosis induced by ox-LDL in cultured neonatal rat cardiomyocytes at least in part by modulating the TLR4/NF-κB signaling pathway.
Highlights
In the present study, we investigated the effect of oxidized low-density lipoprotein (ox-LDL) on cardiomyocyte apoptosis
To confirm the apoptosis-inducing effect of ox-LDL, the cultured cardiomyocytes were incubated with different concentrations of ox-LDL (0, 10, 50, 100 mg/L) for 24 h or with 50 mg/L ox-LDL for 0, 6, 12 and 24 h respectively at identical environment, and cell apoptosis study was conducted by flow cytometry assay
The results showed that ox-LDL caused cardiomyocytes apoptosis in a dose- and time-dependent manner (Fig. 1), which provide information about the suitable concentration of ox-LDL for further studies
Summary
We investigated the effect of ox-LDL on cardiomyocyte apoptosis. We found that ox-LDL induced cardiomyocytes apoptosis via TLR4/NF-κB signaling pathway and inhibition of TLR4 signal transduction by resatorvid (TAK-242) significantly suppressed ox-LDL-induced cardiomyocyte apoptosis. Our results reveal the signaling transduction of ox-LDL-induced cardiomyocyte apoptosis, and inhibition of TLR4 signaling pathway may provide new therapeutic options for myocardial injury in atherosclerotic cardiovascular diseases
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