The Ratio of Unesterified/esterified Cholesterol is the Major Determinant of Atherogenicity of Lipoprotein Fractions

Abstract

BackgroundThe hypothesis is proposed that the atherogenicity of lipoporotein fractions is correlated with the content of unesterified cholesterol.ObjectivesTo evaluate the role and prognostic values of unesterified and esterified cholesterol in lipoprotein fractions for coronary artery disease (CAD).Design and methodsThe study population consisted of 400 patients who were divided to CAD controls and cases according to the data of coronary angiography. Fractional cholesterol esterification (FCE) as well as the complete profile of lipids and (apo)lipoproteins were determined.ResultsTotal cholesterol was increased significantly in CAD patients (196.3 ± 52.3 mg/dL vs. 185.7 ± 48.0, p≤ 0.049) and the increment occurred totally in unesterified portion (77.2 ± 28.4 mg/dL vs. 71.1 ± 24.4, p≤ 0.031). HDL cholesterol showed a significant decrease in CAD group (39.9 ± 9.5 mg/dL vs. 44.6 ± 10.5, p≤ 0.001), but the decrement occurred wholly in the esterified portion (26.2 ± 9.2 mg/dL vs. 31.1 ± 8.1, p≤ 0.001). NonHDL cholesterol was increased significantly in CAD group (156.8 ± 48.3 mg/dL vs. 140.3 ± 43.6, p≤ 0.001), and the changes occurred in both un- and esterified portions. FCE in HDL was diminished significantly in CAD patients (64.8 ± 13.9% vs. 69.3 ± 7.9, p≤ 0.01). In multivariate logistic regression analysis, unesterified cholesterol in NonHDL (UeNonHDLc) and esterified cholesterol in HDL (EsHDLc) excluded total cholesterol and HDLc respectively from the regression equation. In ROC analysis, the ratio of UeNonHDLc/EsHDLc was the strongest predictor for CAD among cholesterol subfractions.ConclusionsThe results confirm that UeNonHDLc is atherogenic and EsHDLc is antiatherogenic and are independent risk factors for CAD.

Monobutyrin Reduces Liver Cholesterol and Improves Intestinal Barrier Function in Rats Fed High-Fat Diets

“…However, it should be mentioned that cholesterol transfer may differ between humans and rats, since rats are naturally deficient in cholesteryl ester transfer protein. Recent data in CAD patients indicated the ratio of unesterified/esterified cholesterol in lipoprotein fractions as a stronger predictor of atherogenicity than other cholesterol subfractions [ 28 ]. Thus, further investigations of the presence of different lipids may reveal potential impact of MB supplementation on cholesterol esterification profile.…”

Exploration of Blood Lipoprotein and Lipid Fraction Profiles in Healthy Subjects through Integrated Univariate, Multivariate, and Network Analysis Reveals Association of Lipase Activity and Cholesterol Esterification with Sex and Age

“…HDL particles contribute the removal of excess free cholesterol from the peripheral tissues and deliver it into the liver for excretion, in a process known as ‘cholesterol reverse transport’ [ 53 , 54 ]. HLD removes LDL, the main catabolic product of VLDL, in vascular space and delivers cholesterol into the tissues [ 55 ]; LDL particles can pass via the intima layer of vascular beds and be taken up by macrophages to make foam cells, thus exerting an atherogenic effect [ 56 ], and esterification of cholesterols plays a key role in this process.…”

Esterification of HDL cholesterol is Decreased in Diabetes Mellitus and CAD and Enhanced Following Treatment with Statins

“…Un-esterified total cholesterol and unesterified HDLc were measured by the same kits but without the enzyme of cholesterol esterase (Pars-Azmon Inc., Tehran). Esterified total cholesterol and esterified HDLc were computed by subtractions of unesterified fractions from total cholesterol and HDLc ( 24 ). Immuno-turbidometric assay was used to measure apoB100 and apoAI ( 26 ).…”

“…Free cholesterol is biologically active form, whereas CE is for storage or transport. We proposed the hypothesis that the atherogenicity of LDL particles may be attributed partly to its unesterified cholesterol, whereas anti-atherogenic activity of HDL may be due to its esterified cholesterol ( 24 ). In spite of the large number of studies on the role of cholesterol, there are limited data on esterified- and unesterified- cholesterol in lipoprotein fractions at different situations.…”