IDL, VLDL, chylomicrons and atherosclerosis

Abstract

In humans with the lipoprotein lipase deficiency disorder large amounts of chylomicrons and large very low-density lipoprotein (VLDL) accumulate in plasma. In spite of this, atherosclerosis does not seem to develop at an accelerated rate, suggesting that these lipoproteins do not promote atherogenesis. In humans with dysbetalipoproteinemia remnant lipoproteins (intermediate density lipoprotein (IDL) plus beta-VLDL) accumulate in plasma and these particles may therefore be the factor causing accelerated atherosclerosis in this disorder. Epidemiological studies in humans suggest that IDL or remnant lipoproteins are predictors of the severity or progression of atherosclerosis. Similar studies in the St. Thomas' Hospital rabbit strain, an animal model with genetically elevated plasma levels of VLDL, IDL and low-density lipoprotein (LDL), showed that IDL or remnant lipoproteins were better predictors of the extent of atherosclerosis than were LDL or VLDL. Studies of lipoprotein/arterial wall interactions have demonstrated that the larger the lipoprotein particle, the lower the influx into intima. Very large VLDL and chylomicrons do not seem to enter intima. Although high-density lipoprotein (HDL) enters intima faster than other lipoproteins, the small HDL particles seem to penetrate the entire arterial wall and leave via lymphatics and vasa vasorum in the outer media and adventitia. In contrast, LDL, and possibly also IDL and smaller VLDL, may only leave the intima via the lumen of the artery. In conclusion, a substantial body of evidence suggests that remnant lipoproteins (IDL and smaller VLDL) share with LDL the potential for promoting atherosclerosis, whereas very large VLDL and chylomicrons do not seem to have this effect.

Menopausal Status and Abdominal Obesity Are Significant Determinants of Hepatic Lipid Metabolism in Women

“…This has not been reported previously and the relevance is not clear as yet, but small rather than large VLDL is implicated in atherosclerosis progression 38. VLDL 2 ‐TG production was higher in postmenopausal women than men matched for plasma TG concentrations24 and as discussed by the authors, VLDL 2 is more efficiently converted to LDL than VLDL 1 .…”

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels

“…Whole-VLDL-particle uptake has also been demonstrated in mice, whereby whole-particle lipoprotein uptake in muscle increases by transgenic expression of catalytically inactive LPL in the presence of active LPL [51,52]. A receptor-independent process [53], further characterised as endothelial transcytosis [54], has been proposed to represent the molecular mechanism of chylomicron uptake. For humans, there is also evidence for whole-lipoprotein-particle uptake [24,19]; based on results with arterio-venous concentration differences of lipoprotein particle constituents, Karpe et al hypothesised that skeletal muscle and adipose tissue are likely to be of importance for removal of chylomicron remnant particles [19].…”

Evidence of increased secretion of apolipoprotein B-48-containing lipoproteins in subjects with type 2 diabetes

“…This is of interest because substantial evidence exists indicating that high levels of intestinederived lipoproteins are associated with increased cardiovascular disease risk (3). Chylomicrons are too large to be able to enter the subendothelial space, but once hydrolyzed by the lipoprotein lipase, chylomicron remnants of ,700 Å are small enough to enter into the intima and to participate in atherosclerotic lesion development (4). Chylomicron remnants have been shown to impair normal endothelial function (5), to be chemically modified, and to accumulate in the subendothelial space in the same way as apoB-100-containing lipoproteins do (6,7).…”