Poster Topical Area: Nutritional Epidemiology
Location: Hall D
Poster Board Number: 741
Macrophages play a critical role in atherosclerosis development by facilitating cholesterol accumulation and increasing inflammatory response. We have synthesized void nanoparticles (V-Nano) and epigallocatechin gallate (EGCG)-loaded nanoparticles (E-Nano). We have also incorporated ligands (oxidized phospholipids) on the surface of V-Nano and E-Nano to make LV-Nano and LE-Nano, respectively, which can target macrophages via binding their CD36 receptors. The objectives of this study are to determine the effects of these nanoparticles on macrophage cholesterol accumulation and inflammation in vitro and in vivo.
Elicited mouse peritoneal macrophages were treated with 1XPBS, free EGCG, E-Nano, LE-Nano, V-Nano and LV-Nano at EGCG dose of 20 µg/mL for 16 hours. Macrophage total cholesterol (TC) and free cholesterol (FC) content was measured using a HPLC system. Gene expression and secretion of inflammatory factors (MCP1, TNFα, IL-6) were measured using real-time PCR and ELISA, respectively. Male LDLr−/− mice were fed an atherogenic diet and were given weekly IV injection of above treatments at dose of 25 mg of EGCG/kg body weight for 22 weeks. Plasma TNFα, IL-6 and MCP-1 concentrations were measured using Quantikine® ELISA kits.
As compared to free EGCG, LE-Nano decreased macrophage TC (9.63%) and FC (34.2%) content, but the difference did not reach statistical significance. As compared to 1XPBS, LE-Nano significantly decreased secretion of MCP-1, TNFα and IL-6 from mouse macrophages. The extent of inhibition was increased by the treatment order of V-Nano, LV-Nano, free EGCG< E-Nano < LE-Nano. But LE-Nano compared to 1XPBS significantly increased macrophage TNFα mRNA levels. No significant difference were found in macrophage MCP-1 and IL-6 mRNA levels among treatment groups. LV-Nano significantly decreased plasma concentrations of MCP-1 (compared to free EGCG) and TNFα (compared to LE-Nano). Plasma IL-6 concentrations did not reach statistical significance among treatments.
LE-Nano decreased macrophage cholesterol content, but did not reach statistical difference. Even though LE-Nano and E-Nano decreased inflammatory factor secretion from mouse peritoneal macrophages, but mice plasma data were not consistent with the macrophage data.
Grant Funding Source: NIH 1R15AT007013
PhD student/ graduate research assistant
Texas Tech University