n‐3 Fatty Acids Decrease Lipoprotein Lipase and Macrophages in the Arterial Wall

Arterial lipoprotein lipase (LpL) content links to LDL‐cholesterol (C) delivery and deposition in the arterial wall, and this is modulated by dietary fatty acids (FA); saturated FA‐rich diets (SAT) induce high LpL in aortic media and this results in higher LDL‐C uptake; LpL and LDL‐C are both reduced by n‐3 FA‐rich diets in mouse models. We now examined roles of specific arterial cells that modulate arterial LpL levels. C57BL/6 mice were fed chow, SAT or n‐3 diets for 12 wk. LpL/cell associations were examined by immunofluorescence. Intravenous heparin was utilized to determine intra‐ or extra‐cellular LpL localization. As opposed to SAT, n‐3 diets markedly reduced LpL and macrophage levels (p<0.05), LpL co‐localized with aortic endothelium. SAT increased both LpL and macrophages by ~ 1‐fold; > 60% of LpL and macrophages co‐localized. An approximate 50% of macrophage‐associated LpL was heparin‐releasable (p<0.05). Thus, arterial LpL is differentially associated with different aortic cells types. A substantial increase of LpL by SAT is extra‐cellular and this contributes to increased LDL ”anchoring”. We hypothesize that n‐3 FA decrease risk of cardiovascular disease, in part, by decreasing arterial macrophage‐associated LpL and LDL‐C deposition early in atherogenesis. This study was supported by NIH grants HL40404 (RJD) and T32‐DK007674 (CLC). Grant Funding Source: NIH