Plasma lathosterol measures rates of cholesterol synthesis and efficiency of dietary phytosterols in reducing the plasma cholesterol concentration

Nunes, V.S.; Ilha, Angela de Oliveira Godoy; Ferreira, Guilherme da Silva; Bombo, Renata de Paula Assis; Afonso, Milessa da Silva; Lavrador, Maria Sílvia Ferrari; Machado, Roberta Marcondes; Nakandakare, Edna Regina; Quintão, Eder Carlos Rocha; Lottenberg, Ana Maria

doi:10.1016/j.clinsp.2022.100028

Cited by 4 publications

(2 citation statements)

References 43 publications

(51 reference statements)

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“…Gas chromatography analysis of serum lathosterol could be identified as the marker of cholesterol synthesis to predict the efficacy of simvastatin in patients with CHD ( 53 ). The highest plasma lathosterol concentration was associated with a lack of response of plasma cholesterol during the phytosterols treatment period ( 54 ). Lathosterol synthesis was decreased in patients with aortic stenosis who had a positive family history of cardiovascular disease and concomitant CHD ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

The impact of hypertension for metabolites in patients with acute coronary syndrome

Feng¹,

Yu²,

Zong³

et al. 2023

Ann Transl Med

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Background Acute coronary syndrome (ACS) is one of the leading causes of death and is often accompanied by hypertension. Methods We investigated whether hypertension affects the metabolism of patients with ACS. Serum samples were provided from healthy controls (HCs; n=26), patients with ACS (n=20), or those patients with ACS complicated with hypertension (HTN, n=21), and all were subjected to non-targeted metabolomics analyses based on gas chromatography-mass spectrometry (GC/MS). Differential metabolites were screened using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA). Kyoto Encyclopedia of Genes and Genomes (KEGG) provided metabolic pathways related to these metabolites. Results Compared to those in the HC group, 12 metabolites were significantly upregulated and 6 significantly downregulated in the ACS group; among these, L-cystine and isocitric acid showed the most obvious differences, respectively. Compared to those in the ACS group, 3 metabolites were significantly upregulated and 2 metabolites were significantly downregulated in the ACS-HTN group, among which oleic acid and chenodeoxycholic acid showed the most marked difference, respectively. The five most prominent metabolic pathways involved in differential metabolites between the ACS and HC groups were arginine biosynthesis; oxidative phosphorylation; alanine, aspartate and glutamate metabolism; citrate cycle; and glucagon signaling pathway. The metabolic pathways between the ACS and ACS-HTN groups were steroid biosynthesis, fatty acid biosynthesis, arginine biosynthesis, primary bile acid biosynthesis, and tyrosine metabolism. Conclusions A comprehensive study of the changes in circulatory metabolomics and the influence of HTN was conducted in patients with ACS. A serum metabolomics test can be used to identify differentially metabolized molecules and allow the classification of patients with ACS or those complicated with HTN.

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Section: Discussionmentioning

confidence: 99%

The impact of hypertension for metabolites in patients with acute coronary syndrome

Feng¹,

Yu²,

Zong³

et al. 2023

Ann Transl Med

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“…Whether the differences obtained between the two traits relate to the function of each sterol in terms of its chemical structure and mode of absorption and elimination is to be further studied using in vitro and in vivo mice models. Of note that in humans the hepatic clearance of campesterol is significant lower than that of beta-sitosterol (37), whereas it is stigmasterol accumulation and not the other two plant sterols that causes cardiac injury in mice (21) Titles and legends to figures. The analysis was performed using linear mixed models that were adjusted for age, sex, total cholesterol, the first four principal components.…”

Section: Abcg5/8 Are the Major Players Across Populations For Both Be...mentioning

confidence: 99%

Genome-Wide Association Study and Meta-Analysis of Phytosterols Identifies a Novel Locus for Serum Levels of Campesterol

Alenbawi,

Al-Sarraj,

Umlai

et al. 2023

Preprint

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Background: Sitosterolemia is a rare inherited disorder caused by mutations in the ABCG5/ABCG8 genes. These genes encode proteins that are involved in the transport of plant sterols (phytosterols) out of the body. Mutations in these genes lead to decreased excretion of phytosterols, which can accumulate in the body and lead to a variety of health problems, including xanthoma formation, atherosclerosis, and premature coronary artery disease. Methods: We conducted the first genome-wide association study (GWAS) in the Middle East/North Africa (MENA) population to identify genetic determinants of plant sterol levels in Qatari people. GWAS was performed on serum levels of β-sitosterol and campesterol measured using the Metabolon platform from the Qatar Biobank Cohort and genome sequence data provided by Qatar Genome Program. Furthermore, a trans-ancestry meta-analysis of data from our Qatari cohort with summary statistics from a previously published large cohort (9,758 subjects) of European ancestry was conducted. Results: Using conditional analysis, we identified two independent single nucleotide polymorphisms (SNPs) associated with β-sitosterol (rs145164937 and rs4299376), and two independent SNPs associated with campesterol (rs7598542 and rs75901165) in the Qatari population in addition to two previously reported variants (rs199689137 and rs4245791). All of them map to the ABCG5/8 locus except rs75901165 which is located within the Intraflagellar Transport 43 (IFT43) gene. The meta-analysis replicated most of the reported variants, and our study provided significant support for the association of variants in SCARB1 and ABO with sitosterolemia. Conclusions: This is the first study to shed light on genetic determinants of phytosterols in the MENA region using a genome-wide association approach. We also established the first polygenic risk score for this trait using the European large cohort study. These findings may have future implications on the personalized treatment of hyperlipidemia in general while showing the importance of building population-specific multi-omics databases.

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Are measurements of non-cholesterol sterols in plasma useful in identifying susceptibility to atherosclerosis?

Quintão¹

2023

Arch Prev Med

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This review discusses the validity of plasma non-cholesterol sterols precursors of cholesterol synthesis and phytosterols in the identification of human atherosclerosis. There is an insufficient demonstration that these sterols are valid methods of measurement of cholesterol metabolism. All markers, including cholestanol, that derive from cholesterol synthesis may only reflect body retention of sterols and not necessarily increased intestinal absorption. Also, in most studies, conventional risk factors of atherosclerosis, such as obesity, diabetes mellitus, gender, and age were not taken into account.

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Plasma lathosterol measures rates of cholesterol synthesis and efficiency of dietary phytosterols in reducing the plasma cholesterol concentration

Cited by 4 publications

References 43 publications

The impact of hypertension for metabolites in patients with acute coronary syndrome

The impact of hypertension for metabolites in patients with acute coronary syndrome

Genome-Wide Association Study and Meta-Analysis of Phytosterols Identifies a Novel Locus for Serum Levels of Campesterol

Are measurements of non-cholesterol sterols in plasma useful in identifying susceptibility to atherosclerosis?

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