Multi-omics study identifies novel signatures of DNA/RNA, amino acid, peptide, and lipid metabolism by simulated diabetes on coronary endothelial cells.
Multi-omics study identifies novel signatures of DNA/RNA, amino acid, peptide, and lipid metabolism by simulated diabetes on coronary endothelial cells.
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DOI：
10.1038/s41598-022-16300-5
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发表时间：
2022-07-14
影响因子：
4.6
通讯作者：
Villarreal, Francisco
中科院分区：
文献类型：
--
作者：
Moreno-Ulloa, Aldo;Delgado-De la Herran, Hilda Carolina;Alvarez-Delgado, Carolina;Mendoza-Porras, Omar;Carballo-Castaneda, Rommel A.;Donis-Maturano, Luis;Villarreal, Francisco
冠状动脉内皮细胞(CAEC)在心血管疾病的发生发展中起着重要作用。在2型糖尿病(T2 DM)患者中，CAEC功能障碍与心血管疾病相关。然而，关于糖尿病环境对这种细胞类型的影响的全面研究很少。本研究描述了在长时间的糖尿病环境(高糖和高胰岛素)下，培养的牛血管内皮细胞发生的分子扰动。用液质联用(LC-MS2)和化学信息学评价代谢产物和肽水平的变化。结果与已发表的基于LC-MS2的定量蛋白质组学在相同的体外模型上进行了整合。我们的发现与其他内皮细胞类型的报道一致，并确定了糖尿病环境下细胞中DNA/RNA、氨基酸、多肽和脂肪代谢的新特征。人工数据检查显示，色氨酸分解代谢和苯丙氨酸、谷胱甘肽和脯氨酸多肽代谢物的生物合成受到干扰。荧光显微镜检测到，在处理的细胞中双核增加，这在使用人CAEC时也会发生。这项多组学研究确定了诱导糖尿病环境中的特殊分子扰动，这可能有助于揭示T2 DM受试者心血管疾病发展的潜在机制。
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.
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影响因子：
4.3
作者：
da Silva RR;Wang M;Nothias LF;van der Hooft JJJ;Caraballo-Rodríguez AM;Fox E;Balunas MJ;Klassen JL;Lopes NP;Dorrestein PC
通讯作者：
Dorrestein PC
影响因子：
9.8
作者：
Elmasri, Harun;Ghelfi, Elisa;Yu, Chen-wei;Traphagen, Samantha;Cernadas, Manuela;Cao, Haiming;Shi, Guo-Ping;Plutzky, Jorge;Sahin, Mustafa;Hotamisligil, Gokhan;Cataltepe, Sule
通讯作者：
Cataltepe, Sule
影响因子：
8.6
作者：
Djoumbou Feunang Y;Eisner R;Knox C;Chepelev L;Hastings J;Owen G;Fahy E;Steinbeck C;Subramanian S;Bolton E;Greiner R;Wishart DS
通讯作者：
Wishart DS
影响因子：
9.8
作者：
Brigstock, David R.
通讯作者：
Brigstock, David R.
影响因子：
10.6
作者：
Forman, Henry Jay;Zhang, Hongqiao;Rinna, Alessandra
通讯作者：
Rinna, Alessandra