Omega-3 (n - 3) fatty acids are emerging as bioactive agents protective against cardiovascular disease. However, their cellular delivery pathways are poorly defined. Here we questioned whether the uptake of it - 3 triglyceride-rich particles (TGRP) is mediated by cell surface proteoglycans (PG) using LDL receptor (LDLR)+/+ and LDLR-/- cell models. LDLR+/+ but not LDLR-/- cells showed higher it - 6 over n - 3 TGRP uptake. Removal of cell Surface proteins and receptors by pronase markedly enhanced the uptake of it - 3 but not n - 6 TGRP. Lactoferrin blockage of apoE-mediated pathways decreased the uptake of n - 6 TGRP by Lip to 85% (p < 0.05) but had insignificant effect on it - 3 TGRP uptake. PG removal by sodium chlorate in LDLR+/+ cells substantially reduced it - 3 TGRP uptake but had little effect on n - 6 TGRP uptake. Thus, while n - 6 TGRP uptake is preferentially mediated by LDLR-dependent pathways, the uptake of n - 3 TGRP depends more on PG and non-LDLR cell surface anchoring. (C) 2010 Elsevier Inc. All rights reserved.