Poster Topical Area: Dietary Bioactive Components
Location: Hall D
Poster Board Number: 388
Objectives: Atherosclerosis is characterized by macrophage foam cell formation and abnormal lipid metabolism and the leading cause of death in the western societies. Evidence now suggests that the foaming of macrophages is a crucial early step in the development of atherosclerosis. Autophagy is a catabolic process that removes unfolded proteins and damaged organelles and helps to main cellular homeostasis. Recent studies have shown that autophagy activation increases cholesterol efflux, inhibits inflammation and prevents atherosclerosis. Blueberry is a polyphenol-rich fruit with known health benefits. However, the physiological functions of bioactive compounds present in blueberry leaf (BBL) remain unexplored. The present study explored the effects of BBL extract on foam cell formation, autophagy activity and cholesterol homeostasis in lipid loaded macrophages.
Methods: RAW 264.7, and bone marrow-derived macrophages (BMDM) were treated without (control) and with LPS (100 ng/ml) and oxLDL (25 µg/ml) for 6-24 h followed by treatment with BBL (10 and 25µg/ml) for an additional 6-24 h. Expression of proteins and genes were analyzed by western blot and QRT-PCR respectively. Oil Red O staining was employed to detect lipid accumulation. Statistical analysis was performed by either student t or ANOVA.
Results: Treatment with BBL extract attenuated LPS and oxLDL mediated induction of foam cell formation in both RAW264.7 and BMDM macrophages. Additionally, BBL extract significantly reduced the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) in macrophage foam cells. Interestingly, expression of proteins implicated in cholesterol efflux (ABCA1) and autophagy (LC3II and ATG5) were significantly induced in BBL treated macrophages. More importantly, treatment with BBL extract increased AMPK phosphorylation and reduced mTORC1 gene expression, two key molecules responsible for autophagy regulation, in LPS and oxLDL loaded macrophages.
Conclusion: Our study indicates that BBL extract attenuates foam cell formation, inhibits apoptosis, and induces autophagy activity by targeting AMPK and mTOR in LPS and oxLDL loaded macrophages. Thus, BBL extract may be an important therapeutic option to prevent and treat atherosclerosis.
Startup Fund,Texas Tech University
MD Khurshidul Zahid
Texas Tech University