The induction of macrophage foam cell formation by chylomicron remnants.
The accumulation of foam cells in the artery wall causes fatty streaks, the first lesions in atherosclerosis. LDL (low-density lipoprotein) plays a major role in foam cell formation, although prior oxidation of the particles is required. Recent studies, however, have provided considerable evidence to indicate that CMRs (chylomicron remnants), which carry dietary lipids in the blood, induce foam cell formation without oxidation. We have shown that CMRs are taken up by macrophages and induce accumulation of both triacylglycerol and cholesterol, and that the rate of uptake and amount of lipid accumulated is influenced by the type of dietary fat in the particles. Furthermore, oxidation of CMRs, in striking contrast with LDL, inhibits, rather than enhances, their uptake and induction of lipid accumulation. In addition, the lipid accumulated after exposure of macrophages to CMRs is resistant to efflux, and this may be due to its sequestration in lysosomes. These findings demonstrate that CMRs induce pro-atherogenic changes in macrophages, and that their effects may be modulated by dietary factors including oxidized fats, lipophilic antioxidants and the type of fat present.
Botham
K M
KM
Department of Veterinary Basic Sciences, The Royal Veterinary College, Royal College Street, London NW1 0TU, UK. kbotham@rvc.ac.uk
Moore
E H
EH
De Pascale
C
C
Bejta
F
F
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D053298:Chylomicron Remnants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D010084:Oxidation-Reduction; D051381:Rats
D053298:Chylomicron Remnants; D005227:Fatty Acids