Programmed cell death protein 4 deficiency suppresses foam cell formation by activating autophagy in advanced glycation end-product low-density lipoprotein-induced macrophages.

BACKGROUND

Advanced glycation end-product is a modified form of low-density lipoprotein (AGE-LDL) and accelerates atherosclerosis through undefined mechanisms. Programmed cell death protein 4 (PDCD4), a transcriptional regulator, plays an important role in the regulation of autophagy. The aim of the present study was to investigate the role of PDCD4 involved in AGE-LDL-induced foam cell formation.

METHODS

The characterization of AGE-LDL was measured by the thiobarbituric assay and agarose gel electrophoresis in vitro. RAW264.7, THP-1 cell line and primary peritoneal macrophages of mice were transfected with shPDCD4 plasmid AGE-LDL-induced foam cell formation was stained by Oil Red, and the levels of autophagy and apoptosis were determined by Western blot analysis. Autophagosome was observed with immunofluorescence microscopy. Mitochondrial membrane potential and autophagic flux were assessed by flow cytometry.

RESULTS

AGE modification resulted in significant reduction of absorbance shown by thiobarbituric assay and augmentation of electrophoresis mobility. Further studies suggest that macrophages exposed AGE-LDL triggered autophagy in the early stage of foam cell formation. PDCD4 deficiency enhanced lipoautophagy but inhibited apoptosis and mitochondria dysfunction. Previous studies have been reported that autophagy is an adaptive response might prevent lesional macrophage apoptosis. In our study, we found PDCD4 deficiency attenuated apoptosis and AGE-LDL-induced foam cell formation relied on increased autophagy.

CONCLUSION

Our data revealed that PDCD4 deficiency can facilitate autophagy and benefit for AGE-LDL-induced foam cell formation.