Apolipoprotein E in VLDL and LDL With Apolipoprotein C‐III is Associated With a Lower Risk of Coronary Heart Disease

Mendivil, Carlos O.; Rimm, Eric B.; Furtado, Jeremy; Sacks, Frank M.

doi:10.1161/jaha.113.000130

Cited by 41 publications

(36 citation statements)

References 36 publications

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“…A number of correlative studies showed a greater incidence of CVD in persons with ApoC-III-rich LDL (38). These correlations using ApoC-III associated with LDL are more complex, as it was also reported that increased ApoE content in LDL fractions with ApoC-III is associated with a lower risk of CVD (39). Nevertheless, the use of an antisense-mediated strategy to target hepatic ApoC-III levels in order to effectively lower plasma TG levels (16,40) could prove to be a valid therapeutic approach for treating subjects with FCS, for which there is now no effective therapy.…”

Section: Discussionmentioning

confidence: 99%

ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors

Gordts¹,

Nock²,

Son³

et al. 2016

Journal of Clinical Investigation

210

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Section: Discussionmentioning

confidence: 99%

ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors

Gordts¹,

Nock²,

Son³

et al. 2016

Journal of Clinical Investigation

210

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“…Findings in proteomics studies showed that apoC-III and apoE are present throughout the range of sizes of HDL that are prepared by ultracentrifugation or gel fi ltration, or by precipitation of apoB lipoproteins (21)(22)(23), and analysis of HDL apolipoprotein correlations suggests speciation. However, it is not settled to what extent apoC-III and apoE defi ne distinct subtypes of apoA-I-containing HDL as they do on the apoB lipoproteins ( 18,19,24 ); whether apoC-III and apoE coexist on HDL as they do on VLDL and LDL ( 18,19,24,25 ); and how they are distributed among smaller-or larger-size apoA-I-containing HDL particles. One study, using immunoaffi nity separation, showed that apoE is present in apoA-I-containing lipoproteins in small and large sizes ( 26 ).…”

Section: Isolation Of Hdl From Plasma By Immunoaffi Nity Chromatographymentioning

confidence: 99%

Obesity favors apolipoprotein E- and C-III-containing high density lipoprotein subfractions associated with risk of heart disease

Talayero

Wang

Furtado

et al. 2014

Journal of Lipid Research

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with an elevated risk of coronary heart disease (CHD) ( 1-5 ). However, evidence from randomized clinical trials that studied drugs that increased HDL-C has not been consistent with the hypothesis that HDL protects against CHD. In large-scale trials of novel cholesteryl ester transfer protein inhibitors, CHD incidence was not reduced despite substantial increases in HDL-C levels ( 6-8 ); trials of estrogen replacement therapy in postmenopausal women did not confi rm a protective effect on CHD despite increases in HDL-C ( 9-11 ); and two recent trials of niacin also failed to show reduction in CHD risk, although the increases in HDL-C were modest ( 12, 13 ). Furthermore, some genetic variation that is associated with high HDL-C concentration is not associated with reduced CHD ( 14 ). This raises questions regarding the effi cacy of HDL-C elevation, in general, as a strategy for CHD prevention.Accumulating evidence indicates that protein composition of HDL may be relevant to the risk of CHD ( 15-17 ). ApoE and apoC-III are found on the surface of both triglyceride-rich lipoproteins (TRLs) and . The concentration of apoE in HDL is an independent predictor of recurrent coronary events ( 15 ). More recently, a proteomic analysis showed greater apoE enrichment in small-size HDL (HDL3) in subjects with established coronary artery disease than in normal controls ( 16 ). Similarly, HDL containing apoC-III independently predicts increased risk of an initial coronary event in separate cohorts of men and women ( 17 ), and a high ratio of apoC-III to apoA-I in HDL predicts recurrent coronary events ( 15 ).Abstract Human HDLs have highly heterogeneous composition. Plasma concentrations of HDL with apoC-III and of apoE in HDL predict higher incidence of coronary heart disease (CHD). The concentrations of HDL-apoA-I containing apoE, apoC-III, or both and their distribution across HDL sizes are unknown. We studied 20 normal weight and 20 obese subjects matched by age, gender, and race. Plasma HDL was separated by sequential immunoaffi nity chromatography (anti-apoA-I, anti-apoC-III, anti-apoE), followed by nondenaturing-gel electrophoresis. Mean HDL-cholesterol concentrations in normal weight and obese subjects were 65 and 50 mg/dl ( P = 0.009), and total apoA-I concentrations were 119 and 118 mg/dl, respectively. HDL without apoE or apoC-III was the most prevalent HDL type representing 89% of apoA-I concentration in normal weight and 77% in obese ( P = 0.01) individuals; HDL with apoE-only was 5% versus 8% ( P = 0.1); HDL with apoC-III-only was 4% versus 10% ( P = 0.009); and HDL with apoE and apoC-III was 1.5% versus 4.6% ( P = 0.004). Concentrations of apoE and apoC-III in HDL were 1.5-2× higher in obese subjects ( P р 0.004). HDL with apoE or apoC-III occurred in all sizes among groups. Obese subjects had higher prevalence of HDL containing apoE or apoC-III, subfractions associated with CHD, whereas normal weight subjects had higher prevalence of HDL without apoE or apoC-III, subfractions with protective association against ...

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“…In an ApoE-knockout mouse model, the in-stent neointimal area or the intimato-media (I/M) ratio was greater compared with wild-type mice 25 . This effect of ApoE is independent from its lipidlowering effect 23 . Although ApoE could play a protective role against injury-induced restenosis in animal models, the relationship between ApoE and ISR has not previously been studied in the general human population.…”

Section: Matrix Metalloproteinases (Mmps) Comprise a Family Of Zinc-dmentioning

confidence: 98%

“…Apolipoprotein E (ApoE) is a small apolipoprotein which serves as a ligand to the low-density lipoprotein (LDL) receptor (LDLR) and the LDL receptor-related protein-1 (LRP1), and plays an essential role in metabolism by promoting cellular uptake of lipoproteins 23 . ApoE also inhibits platelet derivated growth factor (PDGF)-induced SMC migration and proliferation and limits neointimal hyperplasia after arterial injury 24 .…”

Section: Matrix Metalloproteinases (Mmps) Comprise a Family Of Zinc-dmentioning

confidence: 99%

Increased levels of MMP-3, MMP-9 and MPO represent predictors of in-stent restenosis, while increased levels of ADMA, LCAT, ApoE and ApoD predict bare metal stent patency

Pleva¹,

Kušnierová²,

Plevová³

et al. 2015

BIOMED PAP

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Aims. We sought to identify biochemical predictors that indicate susceptibility to in-stent restenosis (ISR) after coronary artery bare-metal stenting. Methods. A total of 111 consecutive patients with post-percutaneous coronary intervention (PCI) in-stent restenosis of a target lesion within 12 months were matched for age, sex, vessel diameter, and diabetes with 111 controls without post-PCI ISR. Plasma or serum levels of biochemical markers were measured: matrix metalloproteinases (MMP) 2, 3, 9; myeloperoxidase (MPO); asymmetric dimethylarginine (ADMA); lipoprotein (a) (Lp[a]); apolipoproteins E and D (ApoE and D); and lecitin-cholesterol acyltransferase (LCAT). Multivariable logistic regression association tests were performed. Results. Increased plasma MMP-3 (OR: 1.013; 95% CI: 1.004-1.023; P = 0.005), MMP-9 (OR: 1.014; 95% CI: 1.008-1.020; P < 0.0001) or MPO (OR: 1,003; 95% CI: 1.001-1.005; P = 0.002) was significantly associated with increased risk of ISR. Increased levels of ADMA (OR: 0.212; 95% CI: 0.054-0.827; P = 0.026), ApoE (OR: 0.924; 95% CI: 0.899-0.951; P < 0.0001), ApoD (OR: 0.919; 95% CI: 0.880-0.959; P = 0.0001), or LCAT (OR: 0.927; 95% CI: 0.902-0.952; P < 0.0001) was associated with risk reduction. No correlation was found between plasma MMP-2 or Lp (a) and ISR risk. Conclusions. Increased levels of MMP-3, MMP-9, and MPO represent predictors of ISR after bare-metal stent implantation. In contrast, increased ADMA, LCAT, and Apo E and D indicate a decreased in-stent restenosis occurrence.

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Apolipoprotein E in VLDL and LDL With Apolipoprotein C‐III is Associated With a Lower Risk of Coronary Heart Disease

Cited by 41 publications

References 36 publications

ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors

ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors

Obesity favors apolipoprotein E- and C-III-containing high density lipoprotein subfractions associated with risk of heart disease

Increased levels of MMP-3, MMP-9 and MPO represent predictors of in-stent restenosis, while increased levels of ADMA, LCAT, ApoE and ApoD predict bare metal stent patency

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