Single-cell transcriptomic, transcriptomic, and metabolomic characterization of human atherosclerosis

Abstract

Background: Atherosclerosis is the main cause of many cardiovascular and cerebrovascular diseases (CVDs), and gaining a deeper understanding of the intercellular connections and key central genes which mediate formation of atherosclerotic plaques is required.Methods: We performed a comprehensive bioinformatics analysis of differential genetic screening, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway annotation, protein-protein interactions (PPIs), pseudo-timing, intercellular communication, transcription factors on carotid single-cell sequencing data, and aortic bulk transcriptome and metabolomic data.Results: Ten cell types were identified in the data: T cells, monocytes, smooth muscle cells, endothelial cells, B cells, fibroblasts, plasma cells, mast cells, dendritic cells, and natural killer cells. Endothelial, fibroblast, macrophage, and smooth muscle cell subtype differentiation trajectories, interaction networks, and important transcription factors were characterized in detail. Finally, using this information combined with transcriptome and metabolome analyses, we found the key genes and signaling pathways of atherosclerosis, especially the advanced glycation end products and receptor for advanced glycation end products signaling pathway (AGE-RAGE signaling pathway) in diabetic complications, linked the differential metabolites with fibroblasts and atherosclerosis and contributed to it in patients with diabetes.Conclusions: Collectively, this study provides key genes, signaling pathways, cellular communication, and transcription factors among endothelial cells, fibroblasts, macrophages, and smooth muscle cells for the study of atherosclerotic plaques, and provides a basis for the diagnosis and treatment of atherosclerosis-like sclerosis.

Mammalian Diaphanous1 signalling in neurovascular complications of diabetes

“…Microarray data supported by subsequent qPCR, immunoblotting and confocal microscopy analyses in aortic tissue and primary cultures of aortic SMC suggested a significant involvement of RAGE in the modulation of the ROCK1 branch of the transforming growth factor‐β (TGF‐β) signalling pathway during atherogenesis. In another study, through an integrated, comprehensive multi‐omics‐based bioinformatics analysis of atherosclerotic plaque combining scRNA‐seq, mRNA‐seq and untargeted metabolomics, Liu et al, 2022 revealed the essential genes and signalling pathways in atherosclerosis (Liu et al, 2022). When changes in differentially expressed genes (DEGs) were mapped onto the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the AGE‐RAGE signalling pathway in diabetic complications emerged among the pathways that had the most critical implications in the process of development of atherosclerotic plaques in fibroblast populations.…”

Identification of metabolic components of carotid plaque in high‐risk patients utilizing liquid chromatography–tandem mass spectrometry

“…Immune cells, vascular smooth muscle cells, lipids, and other components are known to play crucial and complementary roles in the progression of the disease, involving the mediation of microenvironmental transformations within the arterial wall 3,5 . Morphologically, carotid plaque formation generally goes through the pathological stages of intra‐arterial intima thickening or preatheroma, atheroma, fibroatheroma, and complex lesions (plaque fissures, hemorrhage, thrombosis), that is, high‐risk plaques 3,6 .…”

“…Immune cells, vascular smooth muscle cells, lipids, and other components are known to play crucial and complementary roles in the progression of the disease, involving the mediation of microenvironmental transformations within the arterial wall. 3,5 Rui Ding and Wenfei Guan contributed equally.…”