Association of apo B lipoproteins with arterial proteoglycans: Pathological significance and molecular basis

Camejo, Germán; Hurt-Camejo, Eva; Wiklund, Olov; Bondjers, Göran

doi:10.1016/s0021-9150(98)00107-5

Cited by 307 publications

(219 citation statements)

References 113 publications

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“…36 Once trapped in the intima, atherogenic lipoproteins become more susceptible to chemical modification such as oxidation, and thus may be more avidly taken up by macrophages, accelerating foam cell formation. 37 To examine this possibility, we compared the binding affinity of apoB-containing particles isolated from both transgenic and control rabbits. The affinity of apoB-containing lipoproteins for biglycans was correlated with both particle size and composition.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis

Ichikawa

Kitajima

Liang

et al. 2004

Laboratory Investigation

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Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Previous studies using transgenic mice and rabbits have demonstrated that high level of LPL activity in adipose and skeletal muscle protects against diet-induced hypercholesterolemia and subsequently prevents aortic atherosclerosis. However, it is unknown, per se, whether increased LPL activity itself is antiatherogenic, or whether the antiatherogenic effect of LPL is dependent upon the LPL lipid-lowering effect. To address this issue, we fed LPL transgenic and littermate rabbits diets containing different amounts of cholesterol (0.3-0.6%) adjusted to maintain their plasma cholesterol concentrations at similarly high levels for 16 weeks. We analyzed their lipoprotein profiles and compared their susceptibility to atherosclerosis. The results showed that the overexpression of LPL in transgenic rabbits reduced remnant lipoproteins (b-VLDL, do1.006 g/ml) but concomitantly led to a significant increase of the large (d ¼ 1.02-1.04 g/ml) and small LDLs (d ¼ 1.04-1.06 g/ml) compared to the amounts in control rabbits. Furthermore, we found that with equally high hypercholesterolemia, transgenic rabbits developed 1.8-fold more extensive aortic atherosclerosis than control rabbits. To examine the hypothesis that altered lipoprotein profiles may be responsible for the enhanced atherosclerosis in transgenic rabbits, we studied the atherogenic properties of apoB-containing lipoproteins in vitro. These studies revealed that small-sized LDLs of transgenic rabbits were more susceptible to copper-induced oxidation and had higher affinity to biglycan than large remnant lipoproteins. We conclude, therefore, that LPL exerts a dual function in terms of its atherogenicity, namely antiatherogenicity, through enhancing receptormediated remnant lipoprotein catabolism and proatherogenicity via the generation of a large amount of smallsized LDLs. At an equal atherogenic-cholesterol level, small and dense LDLs are more atherogenic than large remnant lipoproteins.

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Section: Discussionmentioning

confidence: 99%

Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis

Ichikawa

Kitajima

Liang

et al. 2004

Laboratory Investigation

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“…Interestingly, Burgess et al (61) noted that a major pool of HepG2 cell surface apoE is associated with chondroitin sulfate proteoglycans. Similarly, there is ample documentation of binding of chondroitin/dermatan sulfate proteoglycan to LDL both in vivo and in vitro (62)(63)(64). In this regard, it is of interest that a basal level of LDL CE selective uptake occurs in the Y1/E/tet/2/3 cells in the absence of apoE expression (Figs.…”

Section: Discussionmentioning

confidence: 99%

The Apolipoprotein E-dependent Low Density Lipoprotein Cholesteryl Ester Selective Uptake Pathway in Murine Adrenocortical Cells Involves Chondroitin Sulfate Proteoglycans and an α2-Macroglobulin Receptor

Swarnakar

Beers

Strickland

et al. 2001

Journal of Biological Chemistry

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Cells acquire lipoprotein cholesterol by receptor-mediated endocytosis and selective uptake pathways. In the latter case, lipoprotein cholesteryl ester (CE) is transferred to the plasma membrane without endocytosis and degradation of the lipoprotein particle. Previous studies with Y1/E/tet/2/3 murine adrenocortical cells that were engineered to express apolipoprotein (apo) E demonstrated that apoE expression enhances low density lipoprotein (LDL) CE uptake by both selective and endocytic pathways. The present experiments test the hypothesis that apoE-dependent LDL CE selective uptake is mediated by scavenger receptor, class B, type I (SR-BI). Surprisingly, SR-BI expression was not detected in the Y1/E/tet/2/3 clone of Y1 adrenocortical cells, indicating the presence of a distinct apoE-dependent pathway for LDL CE selective uptake. ApoE-dependent LDL CE selective uptake in Y1/E/tet/2/3 cells was inhibited by receptor-associated protein and by activated ␣ 2 -macroglobulin (␣ 2 M), suggesting the participation of the LDL receptor-related protein/␣ 2 M receptor. Reagents that inhibited proteoglycan synthesis or removed cell surface chondroitin sulfate proteoglycan completely blocked apoE-dependent LDL CE selective uptake. None of these reagents inhibited SR-BI-mediated LDL CE selective uptake in the Y1-BS1 clone of Y1 cells in which LDL CE selective uptake is mediated by SR-BI. We conclude that LDL CE selective uptake in adrenocortical cells occurs via SR-BI-independent and SR-BI-dependent pathways. The SR-BI-independent pathway is an apoE-dependent process that involves both chondroitin sulfate proteoglycans and an ␣ 2 M receptor.

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“…[12][13][14] The retention and aggregation of LDL (agLDL) in the arterial intima, facilitated by the proteoglycans that conform the extracellular matrix, is a key event in atherogenesis. 15,16 We have recently demonstrated that agLDLs induce high intracellular cholesteryl ester accumulation through LDL receptor-related protein (LRP) uptake in human VSMCs. [17][18][19] Additionally, agLDL upregulates LRP expression in a time-and dose-dependent manner.…”

mentioning

confidence: 99%

Aggregated Low-Density Lipoprotein Uptake Induces Membrane Tissue Factor Procoagulant Activity and Microparticle Release in Human Vascular Smooth Muscle Cells

et al. 2004

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Association of apo B lipoproteins with arterial proteoglycans: Pathological significance and molecular basis

Cited by 307 publications

References 113 publications

Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis

Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis

The Apolipoprotein E-dependent Low Density Lipoprotein Cholesteryl Ester Selective Uptake Pathway in Murine Adrenocortical Cells Involves Chondroitin Sulfate Proteoglycans and an α2-Macroglobulin Receptor

Aggregated Low-Density Lipoprotein Uptake Induces Membrane Tissue Factor Procoagulant Activity and Microparticle Release in Human Vascular Smooth Muscle Cells

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