Chronic kidney disease delays VLDL-apoB-100 particle catabolism: potential role of apolipoprotein C-III

Chan, Doris; Dogra, Gursharan; Irish, Ashley; Ooi, Esther M.M.; Barrett, P. Hugh R.; Chan, Dick C.; Watts, Gerald F.

doi:10.1194/jlr.p900003-jlr200

Cited by 71 publications

(55 citation statements)

References 44 publications

(37 reference statements)

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“…In nephrectomized rats with chronic renal failure, the expression of hepatic LRP has been shown to be down-regulated 61) . Reduced hepatic LRP activity could potentially contribute to the impaired clearance and increased concentrations of CM-remnant and IDL-remnant particles, as well as hypertriglyceridemia observed in CKD patients 50,62) . The clearance of VLDL and IDL remnants in CKD patients could also be affected by a novel pathway of clearance via the VLDL receptor described in adipocytes and myocytes of rabbits 63) .…”

Section: Abnormalities Of Apoa-containing Lipoproteinsmentioning

confidence: 99%

“…It has also been suggested that the accumulation of triglyceride-rich atherogenic lipoproteins in the circulation, as a result of deficient LPL activity, may also limit the delivery of lipid fuel by these triglyceride-rich lipoproteins to adipocytes and myocytes, possibly predisposing ESRD patients to the development of cachexia and decreased exercise capacity 26) . Elevated levels of apoC-Ⅲ, a potent inhibitor of LPL, occur in these patients and may further contribute to the suppressed lipolysis of triglyceride-rich VLDL and CM by LPL, subsequently reducing particle uptake 50,51) . ApoC-Ⅲ also appears to modulate apoB-lipoprotein removal by suppressing the binding of lipoprotein remnants to LDL-receptor-related protein.…”

Section: Liver and Intestinal Metabolism Of Tgrlmentioning

confidence: 99%

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Lipid Abnormalities in Patients with Chronic Kidney Disease: Implications for the Pathophysiology of Atherosclerosis

Keane

Tomassini

Neff

2013

JAT

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Cardiovascular disease is increased in patients with chronic kidney disease (CKD) and is the principle cause of morbidity and mortality in these patients. In patients with stage 5 CKD, structural changes in the myocardium have been implicated as the principle cardiovascular processes leading to this increase in morbidity and mortality, while atherosclerotic events including acute myocardial infarction and strokes are responsible for approximately 10-15% of cardiovascular deaths. Dyslipidemia is common in CKD patients and is usually not characterized by elevated cholesterol levels, except in patients with marked proteinuria. Increased triglyceride levels in conjunction with decreased highdensity lipoprotein levels are the commonest qualitative abnormality. Characteristically, abnormalities in the metabolism of apolipoprotein (apo) B-containing lipoproteins have been described, including both gut derived (apoB-48) as well as those produced by hepatic synthesis (apoB-100). A decrease in enzymatic delipidation as well as reduced receptor removal of these lipoproteins both contribute to the increased levels of these apo-B-containing particles and their remnants (which are believed to be highly atherogenic). Abnormalities in the metabolism of apoA-containing lipoproteins are also present and these changes contribute to the lower levels of HDL seen. Qualitative abnormalities of these HDL particles may be associated with cellular oxidative injury and contribute to a proinflammatory, pro-thrombotic milieu that is frequently present in CKD patients. J Atheroscler

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Section: Abnormalities Of Apoa-containing Lipoproteinsmentioning

confidence: 99%

Section: Liver and Intestinal Metabolism Of Tgrlmentioning

confidence: 99%

Lipid Abnormalities in Patients with Chronic Kidney Disease: Implications for the Pathophysiology of Atherosclerosis

Keane

Tomassini

Neff

2013

JAT

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“…Laboratory methods for measurements of lipids, lipoproteins, and other biochemical analytes have been previously detailed ( 10 ). Insulin resistance was calculated using a homeostasis model assessment (HOMA) score.…”

Section: Biochemical Analysesmentioning

confidence: 99%

Plasma apolipoprotein C-III metabolism in patients with chronic kidney disease

Ooi

Chan

Watts

et al. 2011

Journal of Lipid Research

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Supplementary key words kinetics • lipoprotein metabolism • triglyceridesCardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD) ( 1 ). While the precise mechanisms for increased CVD risk are unknown, both traditional and novel CVD risk factors have been implicated ( 1, 2 ). Dyslipidemia, a well-established risk factor for CVD in the general population, is highly prevalent in CKD ( 3, 4 ). The most frequent dyslipoproteinemic phenotype patterns are elevated plasma concentrations of triglycerides and increased numbers of atherogenic triglyceride-rich lipoprotein (TRL) particles, particularly VLDL and intermediate-density lipoprotein (IDL) ( 3, 4 ). The regulation of TRL metabolism in CKD, however, is poorly understood.Apolipoprotein C-III (apoC-III) is an 8.8 kDa glycoprotein synthesized by the liver and intestines ( 5 ). ApoC-III is highly associated with hypertriglyceridemia and is a powerful independent predictor of CVD risk in subjects without renal disease ( 5 ). In the circulation, apoC-III is associated with TRL and HDL exchanging rapidly between these lipoproteins ( 6 ). In vitro studies demonstrate that apoC-III Abstract Moderate chronic kidney disease (CKD) (defi ned by an estimated glomerular fi ltration rate of 30-60 ml/min) is associated with mild hypertriglyceridemia related to delayed catabolism of triglyceride-rich lipoprotein particles. Altered apolipoprotein C-III (apoC-III) metabolism may contribute to dyslipidemia in CKD. To further characterize the dyslipidemia of CKD, we investigated the kinetics of plasma apoC-III in 7 nonobese, nondiabetic, non-nephrotic CKD subjects and 7 age-and sex-matched healthy controls, using deuterated leucine ([5, 5, 5, 2 H 3 ]leucine), gas chromatography-mass spectrometry, and multicompartmental modeling. Compared with controls, CKD subjects had higher concentrations of plasma and VLDL triglycerides and plasma and VLDL apoC-III ( P < 0.05). The increased plasma apoC-III concentration was associated with a decreased apoC-III fractional catabolic rate (FCR) (1.21 ± 0.15 vs. 0.74 ± 0.12 pools/day, P = 0.03). There were no differences between apoC-III production rates of controls and those of CKD subjects. In CKD subjects, plasma apoC-III concentration was signifi cantly and negatively correlated with apoC-III FCR ( r = ؊ 0.749, P = 0.05) but not with apoC-III production rate. Plasma apoC-III concentration was positively correlated with plasma and VLDL triglycerides and VLDL apoB concentrations and negatively correlated with VLDL apoB FCR ( P < 0.05 for all). ApoC-III FCR was negatively correlated with plasma and VLDL triglycerides and VLDL apoB concentration and positively correlated with VLDL apoB FCR ( P < 0.05 for all). Altered plasma apoC-III metabolism is a feature of dyslipidemia in moderate CKD. Modifi cation of apoC-III catabolism may be an important therapeutic target for reducing cardiovascular disease risk in moderate

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“…Apolipoprotein C-Ⅲ (ApoC-Ⅲ) has been shown to inhibit the LPL and hepatic triglyceride lipase (HTGL) activity as well as the uptake of TRLs and CM-Rs by hepatic lipoprotein receptors 24) . The plasma apoC-Ⅲ concentrations are significantly elevated in patients with CKD 25) . Unfortunately, we did not measure other apolipoproteins, although it is suspected that these changes may hydrolyze CM particles insufficiently, resulting in an A stepwise multiple regression analysis was used to determine eGFR with the p value-to-enter and p value-to-remain set at 0.20.…”

Section: 1751mentioning

confidence: 99%

Serum Apolipoprotein B-48 Concentration Is Associated with a Reduced Estimated Glomerular Filtration Rate and Increased Proteinuria

Okubo

Hanada

Matsui

et al. 2014

JAT

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Chronic kidney disease delays VLDL-apoB-100 particle catabolism: potential role of apolipoprotein C-III

Cited by 71 publications

References 44 publications

Lipid Abnormalities in Patients with Chronic Kidney Disease: Implications for the Pathophysiology of Atherosclerosis

Lipid Abnormalities in Patients with Chronic Kidney Disease: Implications for the Pathophysiology of Atherosclerosis

Plasma apolipoprotein C-III metabolism in patients with chronic kidney disease

Serum Apolipoprotein B-48 Concentration Is Associated with a Reduced Estimated Glomerular Filtration Rate and Increased Proteinuria

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