NMR-based metabolomic profile of hypercholesterolemic human sera: Relationship with in vitro gene expression?
Manuela GrimaldiAngelica PalisiCarmen MarinoPaola MontoroAnna CapassoSara NoviMario Felice TecceAnna Maria D'UrsiPublished in: PloS one (2020)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- cardiovascular disease
- endothelial cells
- gene expression
- magnetic resonance
- high resolution
- cell death
- type diabetes
- endoplasmic reticulum stress
- cell proliferation
- dna methylation
- metabolic syndrome
- mass spectrometry
- transcription factor
- binding protein
- cardiovascular events
- newly diagnosed
- cardiovascular risk factors
- cell wall