Dietary compound quercitrin dampens VEGF induction and PPARgamma activation in oxidized LDL-exposed murine macrophages: association with scavenger receptor CD36.
Oxidized LDL (oxLDL) has been implicated in the pathogenesis of atherosclerosis accompanying lipid-laden cell appearance, inflammatory responses, and vascular dysfunction. This study examined the potentials of polyphenol quercitrin to inhibit oxLDL induction of scavenger receptor A (SR-A) and CD36 involving activation of peroxisome proliferator-activated receptor gamma (PPARgamma). J774A1 murine macrophages were cultured with 10 microg/mL Cu(2+)-oxLDL for various times in the presence of 1-10 micromol/L quercitrin. Cu(2+)-oxLDL at the given concentration facilitated macrophage proliferation and enhanced oxLDL uptake. Quercitrin dampened oxLDL uptake and lipid accumulation elevated in macrophages exposed to oxLDL. Western blot analysis revealed that 10 microg/mL oxLDL upregulated expression of SR-A and CD36, which was rapidly abolished at the transcriptional levels by 10 micromol/L quercitrin within 4 h. Quercitrin diminished production of proinflammatory and proatherogenic vascular endothelial growth factor that augmented through the oxLDL binding to CD36. Similarly, quercitrin repressed expression of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 involved in monocyte trafficking and macropahage migration. In addition, quercitrin attenuated oxLDL-induced transcriptional activation of PPARgamma leading to CD36 induction. Furthermore, quercitrin alleviated macrophage uptake of oxLDL through interfering with PKC-PPAR signaling cascades. These results demonstrate that quercitrin blocked oxLDL uptake, cholesterol influx and lipid-laden foam cell formation through inhibiting induction of SR and VEGF linked to PKCalpha-PPARgamma-responsive pathways. Therefore, quercitrin may be an antiatherogenic agent blocking foam cell formation pertaining to induction of SR and VEGF.
Choi
Jung-Suk
JS
Department of Food and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon, Korea.
Bae
Ji-Young
JY
Kim
Dong Shoo
DS
Li
Jing
J
Kim
Jung-Lye
JL
Lee
Yong-Jin
YJ
Kang
Young-Hee
YH
D000818:Animals; D018955:CD36 Antigens / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D047495:PPAR gamma / Q000276:immunology*; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D042461:Vascular Endothelial Growth Factor A; C099252:oxidized low density lipoprotein; C012526:quercitrin; D011794:Quercetin