D4F alleviates macrophage-derived foam cell apoptosis by inhibiting CD36 expression and ER stress-CHOP pathway.

This study was designed to explore the protective effect of D4F, an apoA-I mimetic peptide, on oxidized LDL (ox-LDL)-induced endoplasmic reticulum (ER) stress-CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) pathway-mediated apoptosis in macrophages. Our results showed that treating apoE knockout mice with D4F decreased the serum ox-LDL level and apoptosis in atherosclerotic lesions with concomitant downregulation of cluster of differentiation 36 (CD36) and inhibition of ER stress. In vitro, D4F inhibited macrophage-derived foam cell formation. Furthermore, like ER stress inhibitor 4-phenylbutyric acid (PBA), D4F inhibited ox-LDL- or tunicamycin (TM, an ER stress inducer)-induced reduction in cell viability and increase in lactate dehydrogenase leakage, caspase-3 activation, and apoptosis. Additionally, like PBA, D4F inhibited ox-LDL- or TM-induced activation of ER stress response as assessed by the reduced nuclear translocation of activating transcription factor 6 and the decreased phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α, as well as the downregulation of glucose-regulated protein 78 and CHOP. Moreover, D4F mitigated ox-LDL uptake by macrophages and CD36 upregulation induced by ox-LDL or TM. These data indicate that D4F can alleviate the formation and apoptosis of macrophage-derived foam cells by suppressing CD36-mediated ox-LDL uptake and subsequent activation of the ER stress-CHOP pathway.

Yao S ，Tian H ，Miao C ，Zhang DW ，Zhao L ，Li Y ，Yang N ，Jiao P ，Sang H ，Guo S ，Wang Y ，Qin S ... -  《-》

Ethanol extract of propolis protects macrophages from oxidized low density lipoprotein-induced apoptosis by inhibiting CD36 expression and endoplasmic reticulum stress-C/EBP homologous protein pathway.

Tian H ，Sun HW ，Zhang JJ ，Zhang XW ，Zhao L ，Guo SD ，Li YY ，Jiao P ，Wang H ，Qin SC ，Yao ST ... -  《BMC Complementary and Alternative Medicine》

Endoplasmic reticulum stress promotes macrophage-derived foam cell formation by up-regulating cluster of differentiation 36 (CD36) expression.

Yao S ，Miao C ，Tian H ，Sang H ，Yang N ，Jiao P ，Han J ，Zong C ，Qin S ... -  《-》

D4F alleviates macrophage-derived foam cell apoptosis by inhibiting the NF-κB-dependent Fas/FasL pathway.

Tian H ，Yao ST ，Yang NN ，Ren J ，Jiao P ，Zhang X ，Li DX ，Zhang GA ，Xia ZF ，Qin SC ... -  《Scientific Reports》

High-density lipoprotein inhibits ox-LDL-induced adipokine secretion by upregulating SR-BI expression and suppressing ER Stress pathway.

Song G ，Wu X ，Zhang P ，Yu Y ，Yang M ，Jiao P ，Wang N ，Song H ，Wu Y ，Zhang X ，Liu H ，Qin S ... -  《Scientific Reports》