NMR-based Metabolomic Profile of Hypercholesterolemic Human Sera: Relationship with in Vitro Gene Expression?

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2020 Apr 17

PMID 32298312

Citations 5

Authors

Manuela Grimaldi

Angelica Palisi

Carmen Marino

Paola Montoro

Anna Capasso

Sara Novi

Mario Felice Tecce

Anna Maria DUrsi

Affiliations

Soon will be listed here.

Abstract

Hypercholesterolaemia is considered an important cause of atherosclerotic cardiovascular disease. In a previous investigation, we demonstrated that cultured hepatoma cells treated with hypercholesterolaemic sera compared with cells treated with normocholesterolaemic sera show overexpression of mRNAs related to mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS2). In the present work, using an NMR metabolomic analysis, we demonstrate that the hypercholesterolaemic blood sera previously used to treat cultured hepatoma cells are characterized by a metabolomic profile that is significantly different from the normocholesterolaemic sera. Acetate, acetone, 2-hydroxybutyrate, cysteine, valine, and glutamine are the metabolites distinguishing the two groups. Abnormalities in the concentrations of these metabolites reflect alterations in energy-related pathways, such as pantothenate and CoA biosynthesis, pyruvate, glycolysis/gluconeogenesis, the citrate cycle, and ketone bodies. Regarding ketone bodies, the pathway is regulated by HMGCS2; therefore, serum samples previously found to be able to increase HMGCS2 mRNA levels in cultured cells also contain higher amounts of the metabolites of its encoded enzyme protein product.

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