Multi-omics study identifies novel signatures of DNA/RNA, amino acid, peptide, and lipid metabolism by simulated diabetes on coronary endothelial cells

Abstract

Coronary artery endothelial cells (CAEC) exert an important role in the development of cardiovascular disease. Dysfunction of CAEC is associated with cardiovascular disease in subjects with type 2 diabetes mellitus (T2DM). However, comprehensive studies of the effects that a diabetic environment exerts on this cellular type are scarce. The present study characterized the molecular perturbations occurring on cultured bovine CAEC subjected to a prolonged diabetic environment (high glucose and high insulin). Changes at the metabolite and peptide level were assessed by Liquid Chromatography–Mass Spectrometry (LC–MS2) and chemoinformatics. The results were integrated with published LC–MS2-based quantitative proteomics on the same in vitro model. Our findings were consistent with reports on other endothelial cell types and identified novel signatures of DNA/RNA, amino acid, peptide, and lipid metabolism in cells under a diabetic environment. Manual data inspection revealed disturbances on tryptophan catabolism and biosynthesis of phenylalanine-based, glutathione-based, and proline-based peptide metabolites. Fluorescence microscopy detected an increase in binucleation in cells under treatment that also occurred when human CAEC were used. This multi-omics study identified particular molecular perturbations in an induced diabetic environment that could help unravel the mechanisms underlying the development of cardiovascular disease in subjects with T2DM.

Metabolomic Analysis of Phytochemical Compounds from Agricultural Residues of Eggplant (Solanum melongena L.)

“…Due to the complexity of describing the entire set of metabolites, we focused our analysis on a select group of metabolites aided by molecular networking and automatic spectral matching as previously described by our group [ 49 , 50 , 51 , 52 ]. Three principal clusters (i.e., groups of metabolites with structural similarity based on MS2) containing terpenes, flavonoid glycosides, and saponins were noted ( Figure 5 ).…”

Metabolomic Profiling of the Responses of Planktonic and Biofilm Vibrio cholerae to Silver Nanoparticles

“…Using GNPS automatic spectral matching we were not able to identify or annotate the metabolites dysregulated by AgNPs because the ones that were annotated were not found to be dysregulated. We, therefore, utilized a data analysis pipeline [ 52 ] that consisted of various advanced in silico annotation tools that allowed us to putatively annotate the metabolites at the molecular structure [ 53 , 54 ] and chemical class levels [ 30 ]. Various compound chemical classes were perturbed, and the abundance and diversity of the compounds were more significantly annotated in the planktonic cells than in the biofilms ( Figure 4 , Figure 5 and Figure 6 ).…”