Apolipoprotein C-III: understanding an emerging cardiovascular risk factor

Ooi, Esther M.M.; Barrett, P. Hugh R.; Chan, Dick C.; Watts, Gerald F.

doi:10.1042/cs20070308

Cited by 240 publications

(211 citation statements)

References 124 publications

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“…The reduction in plasma triglyceride concentrations was chiefly explained by the decrease in VLDL apoC-III concentrations. This is consistent with previous observations that reduced apoC-III in TRL enhances LPL-mediated lipolysis and receptor-mediated clearance of TRL, thereby lowering plasma triglyceride levels (4).…”

Section: Discussionsupporting

confidence: 93%

“…In normolipidemic subjects, the majority of plasma apoC-III is bound to HDL, while in hypertriglyceridemic subjects, the majority is bound to TRL (4). ApoC-III inhibits LPL activity and TRL remnant uptake by hepatic lipoprotein receptors (4). Elevated plasma apoC-III concentration, and specifically its accumulation in TRL and their remnants, is causally related to hypertriglyceridemia in the metabolic syndrome (6).…”

mentioning

confidence: 99%

“…ApoC-III is highly associated with hypertriglyceridemia and is a powerful independent predictor of cardiovascular disease risk (4). In circulation, apoC-III is associated with TRL and HDL, exchanging rapidly between these particles (5).…”

mentioning

confidence: 99%

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Dose-Dependent Effect of Rosuvastatin on VLDL–Apolipoprotein C-III Kinetics in the Metabolic Syndrome

et al. 2008

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OBJECTIVE -Dysregulated apolipoprotein (apo)C-III metabolism may account for hypertriglyceridemia and increased cardiovascular risk in the metabolic syndrome. This study investigated the dose-dependent effect of rosuvastatin on VLDL apoC-III transport in men with the metabolic syndrome.RESEARCH DESIGN AND METHODS -Twelve men with the metabolic syndrome were studied in a randomized double-blind crossover trial of 5-week intervention periods with placebo, 10 mg rosuvastatin, or 40 mg rosuvastatin, with 2-week placebo washouts between each period. VLDL apoC-III kinetics were examined using a stable isotope method and compartmental modeling at the end of each intervention period.RESULTS -Compared with placebo, there was a significant dose-dependent reduction with rosuvastatin in plasma triglyceride and VLDL apoC-III concentrations. Rosuvastatin significantly (P Ͻ 0.05) increased VLDL apoC-III fractional catabolic rate (FCR) and decreased its production rate, with a significant (P Ͻ 0.05) dose-related effect. With 40 mg rosuvastatin, changes in VLDL apoC-III concentration were inversely associated with changes in VLDL apoC-III FCR and positively associated with VLDL apoC-III production rate (P Ͻ 0.05). Changes in VLDL apoC-III concentration and production rate were positively correlated with changes in VLDL apoB concentration and production rate and inversely correlated with VLDL apoB FCR (P Ͻ 0.05). Similar associations were observed with 10 mg rosuvastatin but were either less or not statistically significant.CONCLUSIONS -In this study, rosuvastatin decreased the production and increased the catabolism of VLDL apoC-III, a mechanism that accounted for the significant reduction in VLDL apoC-III and triglyceride concentrations. This has implications for the management of cardiometabolic risk in obese subjects with the metabolic syndrome.

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Section: Discussionsupporting

confidence: 93%

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confidence: 99%

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Dose-Dependent Effect of Rosuvastatin on VLDL–Apolipoprotein C-III Kinetics in the Metabolic Syndrome

et al. 2008

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“…The increase in TG production may be due to excess FFA returning to the liver, particularly in the setting of visceral obesity and insulin resistance, and increased de novo TG production due to hyperinsulinemia [46][47][48]. In hypertriglyceridemia, more VLDL particles, as measured by apoB, and larger and more TG-and apoC-III-enriched lipoproteins are found [49][50][51]. Hepatic insulin resistance may contribute to a high production rate of VLDL because insulin reduces apoB synthesis and VLDL secretion in the liver [52,53].…”

Section: Hypertriglyceridemia As a Major Component Of Atherogenic Dysmentioning

confidence: 99%

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Tenenbaum

Klempfner

Fisman

2014

Cardiovasc Diabetol

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The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG. Initial experience with en ezetimibe/fibrates combination seems promising. The recently released IMPROVE-IT Trial is the first to prove that adding a non-statin drug (ezetimibe) to a statin lowers the risk of future CV events. In conclusion, the classical clinical paradigm of lipids-modifying treatment should be changed and high TG should be recognized as an important target for therapy in their own right. Hypertriglyceridemia should be treated.

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“…8 Apolipoprotein C-III (apoC-III) is synthesized by the liver and to a lesser extent by the intestine. 10 In healthy individuals, plasma apoC-III is mainly present in TRL (VLDL and chylomicrons) and HDL and is redistributed from HDL to TRL in the postprandial state. 11 Indeed, rapid exchanges occur between these particles, although nonexchangeable pools of TRL-apoC-III and HDL-apoC-III have been described.…”

Section: Introductionmentioning

confidence: 99%

Impact of bariatric surgery on apolipoprotein C-III levels and lipoprotein distribution in obese human subjects

Maraninchi¹,

Padilla²,

Béliard

et al. 2017

Journal of Clinical Lipidology

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BACKGROUND: Elevated apolipoprotein C-III (apoC-III) has been postulated to contribute to the atherogenic dyslipidemia seen in obesity and insulin-resistant states, mainly by impairing plasma triglyceride-rich lipoprotein (TRL) metabolism. Bariatric surgery is associated with improvements of several obesity-associated metabolic abnormalities, including a reduction in plasma triglycerides (TGs) and an increase in plasma high-density lipoprotein cholesterol (HDL-C).OBJECTIVES: We investigated the specific effect of bariatric surgery on apoC-III concentrations in plasma, non-HDL, and HDL fractions in relation to lipid profile parameters evolution.METHODS: A total of 132 obese subjects undergoing bariatric surgery, gastric bypass (n 5 61) or sleeve gastrectomy (n 5 71), were studied 1 month before surgery and 6 and 12 months after surgery.RESULTS: Plasma apoC-III, non-HDL-apoC-III, and HDL-apoC-III concentrations were markedly reduced after surgery and strongly associated with reduction in plasma TG. This decrease was E-mail address: rvalero@mail.ap-hm.fr accompanied by a redistribution of apoC-III from TRL to HDL fractions. In multivariate analysis, plasma apoC-III was the strongest predictor of TG reduction after surgery, and the increase of HDL-C was positively associated with plasma adiponectin and negatively with body mass index.CONCLUSION: Marked reduction of apoC-III and changes in its distribution between TRL and HDL consistent with a better lipid profile are achieved in obese patients after bariatric surgery. These apoC-III beneficial modifications may have implications in dyslipidemia improvement and contribute to cardiovascular risk reduction after surgery.

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Apolipoprotein C-III: understanding an emerging cardiovascular risk factor

Cited by 240 publications

References 124 publications

Dose-Dependent Effect of Rosuvastatin on VLDL–Apolipoprotein C-III Kinetics in the Metabolic Syndrome

Dose-Dependent Effect of Rosuvastatin on VLDL–Apolipoprotein C-III Kinetics in the Metabolic Syndrome

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

Impact of bariatric surgery on apolipoprotein C-III levels and lipoprotein distribution in obese human subjects

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