ApoC-III content of apoB-containing lipoproteins is associated with binding to the vascular proteoglycan biglycan

Olin-Lewis, Katherine; Krauss, Ronald M.; Belle, Michael La; Blanche, Patricia J.; Barrett, P. Hugh R.; Wight, Thomas N.; Chait, Alan

doi:10.1194/jlr.m200322-jlr200

Cited by 95 publications

(49 citation statements)

References 50 publications

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“…However, reduced binding to heparan sulfate proteoglycan of VLDL apoC-III could also operate at the hepatocyte surface and be a mechanism for decreased receptor-mediated uptake and reduced clearance, as found in our study. In another study, in vitro, apoC-III content of apoB lipoproteins in humans was associated with increased binding affinity to vascular proteoglycan biglycan (36). Thus, these divergent findings from distinct model systems do not provide a conclusion regarding whether VLDL metabolism is affected by apoC-III interacting with vascular proteoglycan.…”

Section: Kinetics Of Apob Lipoproteins According To Apoc-iii and Apoementioning

confidence: 74%

“…Upstream pathways include the activation of protein kinase C, RhoA, and nuclear factor-kB, all of which could have proinflammatory effects on cells in developing atheromatous lesions. Furthermore, apoC-III may also increase the binding of apoB lipoproteins to vascular proteoglycan biglycans (36), an action that would increase the retention of apoB lipoproteins in the arterial wall. Thus, the abundance of apoC-III on TRLs may be a crucial factor in explaining their atherogenicity.…”

Section: Kinetics Of Apob Lipoproteins According To Apoc-iii and Apoementioning

confidence: 99%

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Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions

Zheng

Khoo

Ikewaki

et al. 2007

Journal of Lipid Research

111

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The atherogenicity theory for triglyceride-rich lipoproteins (TRLs; VLDL 1 intermediate density lipoprotein) generally cites the action of apolipoprotein C-III (apoC-III), a component of some TRLs, to retard their metabolism in plasma. We studied the kinetics of multiple TRL and LDL subfractions according to the content of apoC-III and apoE in 11 hypertriglyceridemic and normolipidemic persons. The liver secretes mainly two types of apoB lipoproteins: TRL with apoC-III and LDL without apoC-III. Approximately 45% of TRLs with apoC-III are secreted together with apoE. Contrary to expectation, TRLs with apoC-III but not apoE have fast catabolism, losing some or all of their apoC-III and becoming LDL. In contrast, apoE directs TRL flux toward rapid clearance, limiting LDL formation. Direct clearance of TRL with apoC-III is suppressed among particles also containing apoE. TRLs without apoC-III or apoE are a minor, slow-metabolizing precursor of LDL with little direct removal. Increased VLDL apoC-III levels are correlated with increased VLDL production rather than with slow particle turnover. Finally, hypertriglyceridemic subjects have significantly greater production of apoC-IIIcontaining VLDL and global prolongation in residence time of all particle types. ApoE may be the key determinant of the metabolic fate of atherogenic apoC-III-containing TRLs in plasma, channeling them toward removal from the circulation and reducing the formation of LDLs, both those with apoC-III and the main type without apoC-III.-Zheng, C., C. Khoo, K. Ikewaki, and F. M. Sacks. Epidemiological studies demonstrate that apolipoprotein C-III (apoC-III) and the apoB lipoproteins that have apoC-III as a component independently predict coronary heart disease (1-3). ApoC-III is present on ?40-80% of triglyceride-rich lipoproteins (TRLs) and ?5-10% of LDLs in plasma (4-6). The mechanisms by which apoC-III causes hypertriglyceridemia and atherosclerosis are incompletely understood.Experiments in vitro show that apoC-III can inhibit lipoprotein lipase (7,8) and hepatic lipase (9) and retard the clearance of VLDL by interfering with the binding of apoB-100 (10) or apoE to hepatic receptors (11, 12). Direct evidence supporting a role of high apoC-III level in abnormal TRL metabolism has come from transgenic animal studies. Overexpression of apoC-III in mice causes hypertriglyceridemia (13-17), whereas apoC-III deficiency protects against it (18,19). In these studies, impaired particle clearance via LDL receptors (14-16), reduced binding affinity to cell surface proteoglycans (15, 17), inhibition of lipolysis (17,19), and overproduction of VLDL triglyceride (14, 16) have all been implicated as mechanisms for the hypertriglyceridemic effect of apoC-III. In humans, there is also evidence for apoC-III affecting TRL metabolism. Patients with combined deficiency of apoC-III and apoA-I experience rapid VLDL clearance (20). In a kinetic study, the plasma concentrations and secretion rates of VLDL apoC-III were correlated with those of VLDL triglycerid...

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Section: Kinetics Of Apob Lipoproteins According To Apoc-iii and Apoementioning

confidence: 74%

Section: Kinetics Of Apob Lipoproteins According To Apoc-iii and Apoementioning

confidence: 99%

Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions

Zheng

Khoo

Ikewaki

et al. 2007

Journal of Lipid Research

111

View full text Add to dashboard Cite

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“…This apparent contradiction with the existing literature must be attributed to at least two facts. First, the content of apoE in LDL(2) is much lower (on average, less than 0.3 molecules of apoE per particle) (16,20) than that of remnant lipoproteins (several molecules per particle) (14); and second, apoE presents high affinity for heparin and heparan sulfate, but its affinity for dermatan sulfate is moderate, and for chondroitin sulfate, very low (47). Indeed, the PGs isolated from human aorta were composed mainly of chondroitin sulfate, and had only low amounts of dermatan sulfate and no heparan sulfate.…”

Section: Discussionmentioning

confidence: 99%

High binding affinity of electronegative LDL to human aortic proteoglycans depends on its aggregation level

Bancells

Benı́tez

Jauhiainen

et al. 2009

Journal of Lipid Research

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Electronegative LDL [LDL (2)] is an atherogenic subfraction of plasma LDL that has increased apolipoprotein E (apoE) and apoC-III content, high density, and increased susceptibility to aggregation. These characteristics suggest that LDL(2) could bind to proteoglycans (PGs); therefore, our aim was to evaluate its affinity to PGs. Binding of LDL(2) and native LDL [LDL(1)] to human aortic PGs was determined by precipitation of LDL-glycosaminoglycan complexes, LDL incubation in PG-coated microtiter wells, and affinity chromatography on PG column. All methods showed that LDL(2) had higher binding affinity to PGs than did LDL(1). PG capacity to bind LDL(2) was increased approximately 4-fold compared with LDL(1) in precipitation and microtiter assays. Chromatography on PG column showed LDL(2) to consist of two subpopulations, one with higher and one with lower PG binding affinity than LDL(1). Unexpectedly, the lower PG affinity subpopulation had increased apoE and apoC-III content. In contrast, the high PG affinity subpopulation presented phospholipase C (PLC)-like activity and increased aggregation. These results suggest that PLC-like activity could alter LDL lipid composition, thereby promoting particle aggregation and binding to PGs. This propensity of a subpopulation of LDL(2) to bind to PGs could facilitate its retention in the extracellular matrix of arterial intima and contribute to atherosclerosis progression.-Bancells, C., S. Benítez, M. Jauhiainen, J. Ordóñez-Llanos, P. T. Kovanen, S. Villegas, J. L. Sánchez-Quesada, and K. Öörni. High binding affinity of electronegative LDL to human aortic proteoglycans depends on its aggregation level. J. Lipid Res. 2009. 50: 446-455.

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“…LDL cholesterol was calculated their retention in the vascular wall, and stimulates production of inflammatory cytokines and adhesion molecules in monocytes and endothelial cells (11)(12)(13). In humans, higher apoC-III concentrations on lipoprotein particles are associated with both atherosclerosis progression and incident coronary artery disease (14)(15)(16)(17).…”

Section: +mentioning

confidence: 99%

Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes

Koška

Yassine

Trenchevska

et al. 2016

Journal of Lipid Research

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ApoC-III content of apoB-containing lipoproteins is associated with binding to the vascular proteoglycan biglycan

Cited by 95 publications

References 50 publications

Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions

Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions

High binding affinity of electronegative LDL to human aortic proteoglycans depends on its aggregation level

Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes

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