Postprandial remnant lipoproteins as targets for the prevention of atherosclerosis.

PURPOSE OF REVIEW: Oxidized low-density lipoprotein (Ox-LDL) and chylomicron remnants were previously proposed as the most atherogenic lipoproteins for the causal lipoproteins of atherosclerosis. However, there are still controversies on these hypothesizes. Therefore, we have proposed a new hypothesis based on our recent findings of remnant lipoproteins (RLPs) in postprandial plasma. RECENT FINDINGS: Plasma RLP-C and RLP-TG increased significantly after fat load. More than 80% of the increased triglycerides after fat load consisted of the triglycerides in RLP, which contained greater amount of apoB100 than apoB48 particles as mostly very low density lipoproteins (VLDL) remnants. The majority of lipoprotein lipase (LPL) in plasma was found in RLP as RLP-LPL complex, which is released into circulation after hydrolysis. LPL activity and concentration in plasma did not increase after food intake associated with the insufficient hydrolysis of chylomicrons and VLDL and resulted in the significant increase of RLP-TG. Plasma LPL was inversely correlated with RLP particle size and number. SUMMARY: VLDL remnants have been shown as the major atherogenic lipoproteins in postprandial plasma associated with LPL activity as the targets for prevention of atherosclerosis. We also proposed a new definition of RLPs, 'LPL bound TG-rich lipoproteins' based on the findings of RLP-LPL complex.

Chylomicron remnants: mediators of endothelial dysfunction?

Vascular disease is initiated by activation of the endothelium characterized by the predominance of pro-inflammatory and pro-coagulant changes in endothelial cells (ECs) referred to collectively as 'endothelial dysfunction'. There is increasing evidence that lipoproteins of dietary origin modulate EC function and the use of artificial chylomicron remnant-like particles (CRLPs) in vitro is now beginning to shed light on the molecular mechanisms through which these particles influence cell behaviour. CRLPs enriched in n-6 PUFAs (polyunsaturated fatty acids) influence the production of vasoactive mediators by ECs in a pro-inflammatory manner. Thus CRLPs reduce the synthesis and release of nitric oxide and alter the balance of release of vasodilator versus vasoconstrictor eicosanoids. These changes are accompanied by induction of cyclo-oxygenase-2 expression and activity as well as increased expression of adhesion molecules and the antioxidant defence enzyme haem oxygenase-1. CRLPs also activate a number of intracellular signalling pathways, including NF-kappaB (nuclear factor kappaB) and MAPKs (mitogen-activated protein kinases), which may be involved in mediating their effects on gene expression. The effects of CRLPs on EC behaviour can also be modulated by the type of fat/oxidation status of the particles. These findings support the hypothesis that lipoproteins of dietary origin directly regulate molecular events in the vascular wall.

Dietary fats induce human monocyte activation in vitro.

In early atherosclerosis the frequency of activated monocytes in the peripheral circulation is amplified, and migration of monocytes into the walls of the aorta and large arteries is increased, due partly to de novo expression or activation of monocyte adhesion molecules. Although there is increasing evidence that CMRs (chylomicron remnants) are strongly atherogenic, the outcomes of interactions between blood monocytes and circulating CMRs are not known. Here, we have studied the effects of CRLPs (CMR-like particles) on THP-1 human monocyte oxidative burst. The particles induced a significant increase in reactive oxygen species within 1 h, which persisted for 24 h. We suggest that monocyte-CMR interactions may be important in early atherosclerosis when many activated monocytes are found in susceptible areas of the artery wall.