Reduced effect on apoptosis of 4-hydroxyhexenal and oxidized LDL enriched with n-3 fatty acids from postmenopausal women

Abstract

Background: Oxidized low-density lipoprotein (oxLDL) promotes apoptosis in atherosclerotic plaques in the vascular wall, a process mediated through its oxidized lipids. 4-Hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE), derived from oxidation of n-6 and n-3 fatty acids, respectively, are among the major oxidized products in oxLDL.Hypothesis: This study hypothesized that eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA)-rich versus linoleic acid-rich oxLDL obtained from postmenopausal women and HNE versus HHE differentially influence apoptosis in U937 cells.Experimental Design: Thirty healthy postmenopausal women were supplemented with 14 g/day safflower oil (SO), 7 g/day of both fish oil and SO (low dose LFO) or 14 g/day fish oil (high dose HFO) for 5 weeks. Low-density lipoprotein, obtained after supplementation, was oxidized with 5 µM CuSO4 at 37°C for 6 h. The concentration of cholesteryl ester hydroperoxides (CEOOH) and conjugated dienes was measured in the oxidized LDL (oxLDL). U937 cells were incubated with the oxLDL, 10 µM of HHE, 7 µM of HHE plus 3 µM of HNE, 5 µM of both HHE and HNE or 10 µM of HNE and the extent of apoptosis measured three ways. Results:The concentration of CEOOH and conjugated dienes in oxLDL did not differ among the three treatment groups. The percent of apoptotic cells was approximately 40% lower when incubated with oxLDL obtained from the HFO-supplemented group than the SO-supplemented group measured by both the Annexin V and the DNA fragmentation assays (P=.04 and .004, respectively). Apoptosis of U937 cells was significantly lower in cells incubated with 10 µM of HHE, and mixtures of HHE and HNE than the 10 µM HNE when measured by the Annexin V, DNA fragmentation and 4,6-diamidino-2-phenylindole (DAPI) staining. Conclusions:These data suggest that the cardioprotective properties of n-3 fatty acids may derive in part from their less reactive oxidized lipid metabolites.

Olive oil and oxidative stress

“…In several randomized intervention studies, but not in all [43,44], x3-PUFA from fish oil increased the susceptibility of LDL to oxidation in front of MUFA-rich [45,46] diets. One study reported differences among omega-3 fatty acids on the susceptibility of LDL to oxidation, with an increase after eicosapentanoate, but not with docosahexanoate-rich oil, when compared with an olive oil rich diet [47].…”

Trans‐4‐hydroxy‐2‐hexenal is a neurotoxic product of docosahexaenoic (22:6; n‐3) acid oxidation

“…2004a,b; Choudhary et al. 2005; Lee and Wander 2005). HHE is a potent inducer of permeability transition in hepatic mitochondria but not mitochondria isolated from brain (Kristal et al.…”

Functional Foods and Nutraceuticals in the Primary Prevention of Cardiovascular Diseases

“…Moreover, fish ingestion has been related to a reduced risk for myocardial infarction, which may relate to beneficial effects of EPA and DHA on plaque stability (probably related to the content of inflammatory cells) and modulation of endothelial function [38]. EPA and DHA have also been shown to lower low-density lipoprotein (LDL) oxidative susceptibility in postmenopausal women, which could help to reduce the risk of CVD [39]. Primary among these is the reduction of serum triglycerides [40].…”