The effect of estrogens and phytoestrogenic lignans on macrophage uptake of atherogenic lipoproteins

Abstract

The present study examined the effect of estrogens and compounds with estrogenic activity on the uptake of atherogenic lipoproteins into macrophages, thought to be the initiating step in the development of atherosclerotic lesions. Isolated low density lipoprotein (LDL) and lipoprotein(a) (Lp(a)) were radiolabelled with (3)H-cholesterol linoleate, and incubated with J774 macrophages for 24 hours in the presence of pharmacological doses of estrogens and phytoestrogens. At a concentration of 0.1 microM, the estrogen 17beta-estradiol significantly reduced LDL uptake by macrophages by 14% (p < 0.05), but estrone did not have any effect. At 10 microM, both estrogens significantly reduced macrophage LDL uptake, but the phytoestrogenic-lignans enterodiol and enterolactone had no effect on LDL uptake. Lp(a) uptake into cells was significantly reduced by both estrone and estradiol, and by enterolactone and enterodiol at concentrations of 10 microM (p < 0.01), with enterodiol being most effective. The results of this study suggest that the uptake of these structurally similar lipoproteins is regulated differently. Macrophage Lp(a) uptake appears more phytoestrogen sensitive than does LDL uptake.

Estrogens and Glucocorticoid Hormones in Adipose Tissue Metabolism

“…In vitro estradiol increased hepatic LDL receptor activity [61], which might be one mechanism mediating the estrogenic LDLlowering effect. Estrogen also attenuates the expression of acutephase proteins from the endothelial cells [62] and decreases the macrophagic accumulation of LDL and Lp(a), a key step in the formation of foam cells and initiation of the atherosclerotic process [63].…”

Low serum enterolactone concentration is associated with low colonicLactobacillus–Enterococcuscounts in men but is not affected by a synbiotic mixture in a randomised, placebo-controlled, double-blind, cross-over intervention study

“…Low serum enterolactone concentration is an independent risk factor of acute coronary events and death for CHD and CVD in men ( 1 , 2 ) . The inhibition of lipid peroxidation ( 3 , 4 ) , up-regulation of hepatic LDL receptor activity ( 5 ) , inhibition of lipoprotein uptake by macrophages ( 6 ) and oestrogen-like effect ( 7 ) are the proposed mechanisms behind the protective effect of enterolactone. Enterolactone is produced by intestinal metabolism of food lignans such as matairesinol, secoisolariciresinol, pinoresinol and lariciresinol ( 8 – 10 ) , non-energetic, phenolic plant compounds abundantly found in whole-grain cereals, vegetables and some fruits and berries ( 10 , 11 ) .…”

Up-Regulation of Bcl-2 through ERK Phosphorylation Is Associated with Human Macrophage Survival in an Estrogen Microenvironment

“…acrophages express estrogen receptor subtypes ␣ and ␤ (1-3) and are therefore capable of responding to increase in estrogen during the follicular phase of menstrual cycle (4), at the time of exposure from exogenous sources such as phytoestrogens (5), following administration for prophylactic and therapeutic purposes (6), or during accidental exposure to estrogenic chemicals (7,8). Estrogen affects a variety of macrophage functions; for example, it can reduce accumulation of cholesteryl esters in macrophages (2), stimulate production of NO (9,10), increase arachidonic acid release (11), regulate activationrelated events (2,12), decrease monocyte adhesion to vasculature (13), enhance macrophage phagocytosis (14), and facilitate Ca 2ϩ influx (10).…”