Dataset Information

Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of Cardiovascular Disease Patients.

ABSTRACT: Shotgun lipidomic analysis of 203 lipids in 13 lipid classes performed on blood plasma of donors who had just suffered an acute coronary syndrome (ACS, n?=?74), or an ischemic stroke (IS, n?=?21), or who suffer from stable angina pectoris (SAP, n?=?78), and an age-matched control cohort (n?=?52), showed some of the highest inter-lipid class correlations between cholesteryl esters (CE) and phosphatidylcholines (PC) sharing a common fatty acid. The concentration of lysophospatidylcholine (LPC) and ratios of concentrations of CE to free cholesterol (Chol) were also lower in the CVD cohorts than in the control cohort, indicating a deficient conversion of Chol to CE in the blood plasma in the CVD subjects. A non-equilibrium reaction quotient, Q', describing the global homeostasis of cholesterol as manifested in the blood plasma was shown to have a value in the CVD cohorts (Q'_ACS?=?0.217?±?0.084; Q'_IS?=?0.201?±?0.084; Q'_SAP?=?0.220?±?0.071) that was about one third less than in the control cohort (Q'_Control?=?0.320?±?0.095, p?-4), suggesting its potential use as a rapid predictive/diagnostic measure of CVD-related irregularities in cholesterol homeostasis.

SUBMITTER: Gerl MJ

PROVIDER: S-EPMC6170447 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of Cardiovascular Disease Patients.

Gerl Mathias J MJ Vaz Winchil L C WLC Domingues Neuza N Klose Christian C Surma Michal A MA Sampaio Júlio L JL Almeida Manuel S MS Rodrigues Gustavo G Araújo-Gonçalves Pedro P Ferreira Jorge J Borbinha Claudia C Marto João Pedro JP Viana-Baptista Miguel M Simons Kai K Vieira Otilia V OV

Scientific reports 20181003 1

Shotgun lipidomic analysis of 203 lipids in 13 lipid classes performed on blood plasma of donors who had just suffered an acute coronary syndrome (ACS, n = 74), or an ischemic stroke (IS, n = 21), or who suffer from stable angina pectoris (SAP, n = 78), and an age-matched control cohort (n = 52), showed some of the highest inter-lipid class correlations between cholesteryl esters (CE) and phosphatidylcholines (PC) sharing a common fatty acid. The concentration of lysophospatidylcholine (LPC) and ...[more]

PMID: 30282999

Similar Datasets

Project description:Identifying the likelihood of a patient having coronary artery disease (CAD) at the time of emergency department (ED) presentation with chest pain could reduce the need for stress testing or coronary imaging after myocardial infarction (MI) has been excluded. The authors aimed to determine if a novel cardiac biomarker consisting of plasma cholesteryl ester (CE) levels typically derived from the activity of the enzyme acyl-CoA:cholesterol acyltransferase (ACAT2) are predictive of CAD in a clinical model.A single-center prospective cohort design enrolled participants with symptoms of acute coronary syndrome (ACS) undergoing coronary computed tomography angiography (CCTA) or invasive angiography. Plasma samples were analyzed for CE composition with mass spectrometry. The primary endpoint was any CAD determined at angiography. Multivariable logistic regression analyses were used to estimate the relationship between the sum of the plasma concentrations from cholesteryl palmitoleate (16:1) and cholesteryl oleate (18:1) (defined as ACAT2-CE) and the presence of CAD. The added value of ACAT2-CE to the model was analyzed comparing the C-statistics and integrated discrimination improvement (IDI).The study cohort was composed of 113 participants with a mean (± standard deviation [SD]) age of 49 (±11.7) years, 59% had CAD at angiography, and 23% had an MI within 30 days. The median (interquartile range [IQR]) plasma concentration of ACAT2-CE was 938 ?mol/L (IQR = 758 to 1,099 ?mol/L) in patients with CAD and 824 ?mol/L (IQR?= 683 to 998 ?mol/L) in patients without CAD (p = 0.03). When considered with age, sex, and the number of conventional CAD risk factors, ACAT2-CE levels were associated with a 6.5% increased odds of having CAD per 10 ?mol/L increase in concentration. The addition of ACAT2-CE significantly improved the C-statistic (0.89 vs. 0.95, p = 0.0035) and IDI (0.15, p < 0.001) compared to the reduced model. In the subgroup of low-risk observation unit patients, the CE model had superior discrimination compared to the Diamond-Forrester classification (IDI = 0.403, p < 0.001).Plasma levels of ACAT2-CE have strong potential to predict a patient's likelihood of having CAD when considered in a clinical model but not when used alone. In turn, a clinical model containing ACAT2-CE could reduce the need for cardiac imaging after the exclusion of MI.

Project description:Macrophages which were incubated with acetylated low-density lipoproteins, resulting in cholesteryl ester accumulation, incorporated the monohydroxyeicosatetraenoic acids (5-, 15-, and 12-HETEs) into cholesteryl esters. The esterification of these hydroxy fatty acids to cholesterol by total membrane preparations of cholesterol-rich macrophages was dependent on the synthesis of the fatty acyl-CoA derivative, and was catalysed by acyl-CoA:cholesterol acyltransferase (ACAT). Stimulation of membrane ACAT activity by 25-hydroxycholesterol increased the synthesis of cholesteryl 12-HETE by 40%. In contrast, inhibiting ACAT activity by progesterone and compound 58-035 decreased cholesteryl 12-HETE production by 60% and 90% respectively. Although 5-, 15- and 12-HETE were esterified to cholesterol by ACAT, these monohydroxy fatty acids were less optimal as substrates compared with oleic acid or arachidonic acid. The hydrolysis and release of 12-HETE and the other monohydroxyeicosatetraenoic acids from intracellular cholesteryl esters and phospholipids occurred at a faster rate than for the more conventional fatty acids, oleate and arachidonate. Cholesteryl esters which contain hydroxy fatty acids therefore provide only a transient storage for lipoxygenase products, as these fatty acids are released into the medium as readily as hydroxy fatty acids found in phospholipids and triacylglycerols. The data provide evidence, for the first time, of an ACAT-dependent esterification of the lipoxygenase products 5-, 15- and 12-HETEs to cholesterol in the macrophage-derived foam cell. The channelling of these monohydroxy fatty acids to cholesteryl esters provides a mechanism which can alter the amount of lipoxygenase products incorporated into cellular phospholipids, thus averting deleterious changes to cell membranes. ACAT, by catalysing the esterification of monohydroxyeicosatetraenoic acids to cholesterol, could play a key role in regulating the amount of lipoxygenase products in the pericellular space of the cholesterol-enriched macrophage.

Dataset Information

Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of Cardiovascular Disease Patients.

Publications

Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of Cardiovascular Disease Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets