Favorable effects of ezetimibe alone or in association with simvastatin on the removal from plasma of chylomicrons in coronary heart disease subjects

Mangili, Otávio Celeste; Gagliardi, Ana Carolina Moron; Mangili, Leonardo Celeste; Mesquita, C.H.; Cesar, Luiz Antônio Machado; Tanaka, Akira; Schaefer, Ernst J.; Maranhão, Raul C.; Santos, Raul D.

doi:10.1016/j.atherosclerosis.2013.12.008

Cited by 17 publications

(9 citation statements)

References 37 publications

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“…Serum lipid analysis was performed with standard commercial kits. The chylomicron-like emulsion labeled with cholesteryl [1- 14 C] oleate (CE) and [9,10- 3 H] glycerol-tri-oleate (TG) was prepared by ultrasonic irradiation, followed by two-step ultracentrifugation, as described previously [ 11 , 12 , 13 ], and then sterilized by passage through a 0.2 micrometer filter. The emulsion was prepared in four batches; each batch was injected in subjects of the both studied groups.…”

Section: Methodsmentioning

confidence: 99%

“…The experimental points of plasma radioactivity measurements at the various sampling times (t, 14 C and 3 H) were fitted to the compartment model shown in Figure 1 . The model proposed by Redgrave and Zech [ 14 ] does not consider a direct output of the compartments (C1) and (C5), but the initial absence of a plateau in the decay curve, as shown previously [ 10 ], suggests that a fraction of the injected particles is removed directly from plasma by the liver or other tissues [ 13 ]. The precision of parameters of the kinetic model presented an averaged coefficient of variation of 4.9%±10.2%.…”

Section: Methodsmentioning

confidence: 99%

“…In this approach, artificially-made emulsions with similar composition to that of lymph chylomicrons and doubly labeled with radioactive cholesteryl esters and triglycerides are intravenously injected. Sequential blood samples are then collected to determine the decay curves of both radioisotopes and fractional clearance rates by compartmental analysis [ 11 , 12 , 13 ]. The curves of cholesteryl esters, that are not independently removed from the emulsion particles, stand for remnant removal.…”

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confidence: 99%

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Removal of Chylomicron Remnants from the Bloodstream is Delayed in Aged Subjects

et al. 2018

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Dietary fats absorbed in the intestine are transported in the circulation as chylomicrons and remnants that have atherogenic potential. Although postprandial lipidemia is increased in older subjects, the specific chylomicron metabolism has not been explored in older subjects nor compared to young subjects, which is the focus of this study. After a 12 h fast, artificially-made emulsions similar to lymph chylomicrons and doubly labeled with radioactive cholesteryl esters and triglycerides were intravenously injected in 23 older (66±4 years) and 20 young (24±3 years) subjects. Sequential blood samples were collected to determine fractional clearance rates (FCR, in min-1) by compartmental analysis. Older subjects had higher LDL-cholesterol (p<0.001) and triglycerides (p<0.0001) than young subjects; HDL-cholesterol presented no difference. The emulsion cholesteryl-ester FCR was lower in older subjects compared to the young (p=0.0001). The emulsion triglyceride FCR did not differ in the two groups. Tested in vitro, however, the lipolysis of the emulsion triglycerides was less intense in the older than in the young subjects. As delayed removal of remnants, indicated by the pronouncedly smaller cholesteryl ester FCR, is related to the presence of cardiovascular diseases, this can be a risk factor which could accelerate atherogenic complications occurring in aged subjects

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Removal of Chylomicron Remnants from the Bloodstream is Delayed in Aged Subjects

et al. 2018

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“…It has been shown that chylomicron remnant-like particles downregulate the pro-inflammatory chemokine and cytokine secretion by monocytes and macrophages [27,28]. More recently, it has been reported that ezetimibe and simvastatin increase the removal of chylomicron-like emulsions from plasma in coronary heart disease subjects [29]. However, the atherogenic mechanisms of chylomicron remnants are not clear.…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 97%

Chylomicron remnant model emulsions induce intracellular cholesterol accumulation and cell death due to lysosomal destabilization

Wakita

Morita

Okamoto

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…When injected into patients with familial hypercholesterolemia, in whom LDLR are defective, LDE was slowly removed, but the plasma clearance increased when patients were treated with statins [6]. On the other hand, the clearance of the nanoparticles was also increased in patients with acute myeloid leukemia [7].…”

Section: Introductionmentioning

confidence: 99%

Tissue Uptake Mechanisms Involved in the Clearance of Non‐Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice

Daminelli

Fotakis

Mesquita

et al. 2017

Lipids

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Lipid core nanoparticles (LDE) resembling LDL behave similarly to native LDL when injected in animals or subjects. In contact with plasma, LDE acquires apolipoproteins (apo) E, A-I and C and bind to LDL receptors. LDE can be used to explore LDL metabolism or as a vehicle of drugs directed against tumoral or atherosclerotic sites. The aim was to investigate in knockout (KO) and transgenic mice the plasma clearance and tissue uptake of LDE labeled with H-cholesteryl ether. LDE clearance was lower in LDLR KO and apoE KO mice than in wild type (WT) mice (p< 0.05). However, infusion of human apoE3 into the apoE KO mice increased LDE clearance. LDE clearance was higher in apoA-I KO than in WT. In apoA-I transgenic mice, LDE clearance was lower than in apoA-I KO and than in apoA-I KO infusion with human HDL. Infusion of human HDL into the apoA-I KO mice resulted in higher LDE clearance than in the apoA-I transgenic mice (p < 0.05). In apoA-I KO and apoA-I KO infused human HDL, the liver uptake was greater than in WT animals and apoA-I transgenic animals (p < 0.05). LDE clearance was lower in apoE/A-I KO than in WT. Infusion of human HDL increased LDE clearance in those double KO mice. No difference among the groups in LDE uptake by the tissues occurred. In conclusion, results support LDLR and apoE as the key players for LDE clearance, apoA-I also influences those processes.

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Favorable effects of ezetimibe alone or in association with simvastatin on the removal from plasma of chylomicrons in coronary heart disease subjects

Cited by 17 publications

References 37 publications

Removal of Chylomicron Remnants from the Bloodstream is Delayed in Aged Subjects

Removal of Chylomicron Remnants from the Bloodstream is Delayed in Aged Subjects

Chylomicron remnant model emulsions induce intracellular cholesterol accumulation and cell death due to lysosomal destabilization

Tissue Uptake Mechanisms Involved in the Clearance of Non‐Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice

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