Inhibition of intestinal cholesterol absorption with ezetimibe increases components of reverse cholesterol transport in humans

Davidson, Michael; Voogt, Jason; Luchoomun, Jayraz; Decaris, J; Killion, Salena; Boban, Drina; Glass, Alexander; Hussein, Mohammad; Lu, Yun; Villegas, Deona; Neese, Richard A.; Hellerstein, Marc K.; Neff, David; Musliner, Thomas; Tomassini, Joanne E.; Turner, Scott

doi:10.1016/j.atherosclerosis.2013.08.006

Cited by 44 publications

(29 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are similar with those of several works completed with other plant extracts, such as the aqueous extract of Dunaliella salina [27] and the ethanolic extract of Crataegus pinnatifida [28], in rats subjected to a feeding regime enriched with lipids. Considering that abnormal lipid profiles constituting the hallmark of HC-induced metabolic syndrome were also prevented in the liver by the extract concomitantly with a marked increase in total cholesterol excreted, we hypothesized that hypolipidemic activity of the extract may be mediated by reducing or inhibiting intestinal cholesterol absorption and increasing reverse cholesterol transport, as observed with agents inducing comparable hypolipidemic effects together with antioxidant effects such as Ezetimibe [29, 30] and bile acid sequestering cholestyramine [22, 31]. This reduction did not reach the normal rate after 4 weeks of treatment and the 4 weeks without treatment what allow us to say that the treatment during 4 weeks could be insufficient, but we noticed a reduction in the rate of VLDL-c during the 4 weeks without treatment, it could be that the extract of C. occidentalis continued to react and to show the effectiveness of the aqueous extract leaves.…”

Section: Discussionmentioning

confidence: 99%

Hypolipidemic, antioxidant and anti-atherosclerogenic effect of aqueous extract leaves of Cassia. occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats

Ntchapda

Barama

Talla

et al. 2017

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundHyperlipidemia and oxidative stress are major risk factors for atherosclerosis, and all three are among the most important risk factors for cardiovascular diseases. Cassia occidentalis aqueous extract has been used in African traditional medicine for the treatment of hypertension and associated cardiovascular diseases. This study was undertaken to evaluate the hypolipidemic and anti-atherosclerotic properties of the aqueous extract of the leaves of C. occidentalis in rats with hypercholesterolemia (HC).Sixty Normocholesterolemic (NC) male rats were divided into six groups (n = 10) and fed a high-cholesterol (HC) diet for 30 days (5 groups), or normal rat chow (normal control group). The plant extract was administered to animals at the increasing dose of 240, 320 and 400 mg/kg. After 4 weeks of treatment 5 rats out of 10 were sacrificed, blood samples, aorta, liver, and fresh faecal were collected and processed for biochemical tests. The experiments were conducted under the same conditions with a group of rat treated with Atorvastatin (1 mg/kg), used positive control. The effects of C. occidentalis on weight gain, water and food consumptions, levels of serum lipids and lipoprotein lipid oxidation and stress markers in blood and liver were also examined.ResultsA significant body weight gain was observed in general in all the group of animals without any treatment after 4 weeks. During the treatment period, the C. occidentalis extract induced a significant increase (P < 0.01) in water consumption and food intakes. After 4 weeks of treatment with hypercholesterolemia, the body temperature and organ weights including the liver, kidney, heart and the testis did not present any significant change. The administration of C. occidentalis extract significantly (p < 0.05) prevented the elevation in TC, LDL-C, VLDL-C, hepatic and aortic TG and TC. The atherogenic, triglycerides, and lipid peroxidation (TBARS) index were also decreased in the rats treated with the plant extract. C. occidentalis favoured the performance of faecal cholesterol. It also significantly inhibited the changes and the formation of aortic atherosclerotic plaques.ConclusionThis study provides evidence of hypolipidemic and antiatherosclerotic effects of C. occidentalis extract. C. occidenntalis aqueous extract reduced bad cholesterols, triglycerides and increasing good cholesterols in rats subjected to a feeding regime enriched with cholesterol. The results support the traditional use of the extract of this plant in the treatment of hypertension and diabetes.

show abstract

Section: Discussionmentioning

confidence: 99%

Hypolipidemic, antioxidant and anti-atherosclerogenic effect of aqueous extract leaves of Cassia. occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats

Ntchapda

Barama

Talla

et al. 2017

BMC Complement Altern Med

View full text Add to dashboard Cite

show abstract

“…Several groups have shown in rodent models in which the biliary pathway should predominate that ezetimibe treatment significantly increases macrophage-to-feces RCT [83,118–120]. Moreover, ezetimibe appears to increase RCT in humans since ezetimibe stimulated the excretion of stable isotope labeled cholesterol that had been IV infused into hyperlipidemic patients [121]. There are two recent studies that have addressed whether ezetimibe increases RCT through the TICE pathway.…”

Section: The New Integrated Model Of Rctmentioning

confidence: 99%

A new model of reverse cholesterol transport: enTICEing strategies to stimulate intestinal cholesterol excretion

Temel

Brown

2015

Trends in Pharmacological Sciences

View full text Add to dashboard Cite

Cardiovascular disease (CVD) remains the largest cause of mortality in most developed countries. Although recent failed clinical trials and Mendelian randomization studies have called into question the high density lipoprotein (HDL) hypothesis, it remains well accepted that stimulating the process of reverse cholesterol transport (RCT) can prevent or even regress atherosclerosis. The prevailing model for RCT is that cholesterol from the artery wall must be delivered to the liver where it is secreted into bile before leaving the body through fecal excretion. However, many studies have demonstrated that RCT can proceed through a non-biliary pathway known as transintestinal cholesterol excretion (TICE). The goal of this review is to discuss the current state of knowledge of the TICE pathway, with emphasis on points of therapeutic intervention.

show abstract

“…24 The rapidly mixing cholesterol pool of 25.3 g in the current study also was similar to the reported pool sizes of 23.4 23 and 25.9 g. 24 The cholesterol flux from the rapidly mixing cholesterol pool out of the body (production rate over the size of the rapidly mixing pool) (4.0%) in the present study was comparable to previous reported values of 4.7% 23 and 4.4%. 24 Others have reported a higher production rate (2.1 g/day) 25 and a lower rapid pool size (11.7 g), 26 probably due to differences in tracer and/or methods used.…”

Section: Discussionmentioning

confidence: 98%

Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima–Media Thickness in Humans

Lin

Racette

et al. 2017

ATVB

View full text Add to dashboard Cite

Objective Epidemiological studies strongly suggest that lipid factors independent of LDL cholesterol contribute significantly to cardiovascular disease (CVD) risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of CVD risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. Approach and Results Cholesterol metabolism and carotid intima-media thickness (CIMT) were quantitated in 86 non-diabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d5 and the nonabsorbable stool marker sitostanol-d4. Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. CIMT was negatively correlated with fecal excretion of endogenous cholesterol (r=−0.426, P<0.0001), total cholesterol (r=−0.472, P=<0.0001), and daily percent excretion of cholesterol from the rapidly-mixing cholesterol pool (r=−0.343, P=0.0012), and was positively correlated with percent cholesterol absorption (r=+0.279, P=0.0092). In a linear regression model controlling for age, sex, systolic blood pressure, hemoglobin A1c, LDL, HDL cholesterol, and statin drug use, fecal excretion of endogenous cholesterol remained significant (P=0.0008). Conclusions Excretion of endogenous cholesterol is strongly, independently, and negatively associated with CIMT. The reverse cholesterol transport pathway comprising the intestine and the rapidly-mixing plasma and tissue cholesterol pool could be an unrecognized determinant of CVD risk not reflected in circulating lipoproteins. Further work is needed to relate measures of reverse cholesterol transport to atherosclerotic disease.

show abstract

Inhibition of intestinal cholesterol absorption with ezetimibe increases components of reverse cholesterol transport in humans

Cited by 44 publications

References 37 publications

Hypolipidemic, antioxidant and anti-atherosclerogenic effect of aqueous extract leaves of Cassia. occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats

Hypolipidemic, antioxidant and anti-atherosclerogenic effect of aqueous extract leaves of Cassia. occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats

A new model of reverse cholesterol transport: enTICEing strategies to stimulate intestinal cholesterol excretion

Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima–Media Thickness in Humans

Contact Info

Product

Resources

About