Quercetin targets VCAM1 to prevent diabetic cerebrovascular endothelial cell injury

Abstract

IntroductionEndothelial cells play important roles in neurodegenerative diseases caused by diabetes, therefore, we aimed at investigating the mechanisms through which endothelial cells are involved in diabetes development.MethodsSingle cell analysis was performed to identify the major endothelial cell subtypes in cardiovascular tissues that are involved in diabetes development. A cell-cell communication approach was then used to identify ligand-receptor interaction pairs between these cell types. Differential expression analysis between the two experimental groups [standard chow diet group and diabetogenic diet with cholesterol (DDC) group] was used to identify diabetes-related differentially expressed genes (DEGs). The upregulated genes were used to identify candidate ligands or receptors, as well as the corresponding cell types. Cell trajectory inference was performed to identify the stage of cell development and changes in expression of candidate ligands or receptors during cell development. Gene set enrichment analysis (GSEA) was conducted to investigate the biological functions of genes of purpose. Finally, molecular dynamics simulations (MDSs) were used to predict potential drugs with the ability to target the proteins of purpose.ResultsSeven cell types, including five endothelial cell subtypes (EC_1, EC_2, EC_3, EC_4, and EC_EndMT), were identified from endothelial cell-enriched single cell samples from the heart and aorta of mice. Cell-cell communication analysis revealed the potential ligand-receptor interactions between these cell types while five important ligand-receptor-associated genes, including Fn1, Vcam1, Fbn1, Col4a1, and Col4a2, were established by differential expression analysis. Among them, Vcam1 is mainly expressed in EC_EndMT and is involved in interactions between EC_EndMT and other cells. Cell trajectory extrapolation analysis revealed a shift from EC_2/EC_4 to EC_EndMT and a shift from EC_EndMT to EC_3/EC_1 during the progression of diabetes. GSEA analysis revealed that upregulation of VCAM1 may have inhibitory effects on cell growth and energy metabolism.ConclusionEC_EndMT subtypes have a complex role in neurodegenerative diseases caused by diabetes. Through mechanisms involved in cell-cell communication, Vcam1 may play an important role in dysregulation of biological functions of EC_ EndMT. Molecular docking results of the quercetin-VCAM1 complex suggest that quercetin may be an effective drug for targeting this protein.

Identification of new markers of angiogenic sprouting using transcriptomics: New role for RND3

“…The data shown here indicate that SNAI1 is activated quickly (1 hr) on collagen matrices and that exposure to S1P and growth factors amplifies this upregulation. Other genes upregulated with invasion that have been previously implicated in EndMT include NDST1 , 106 RND3 , 107 SEMA7A , 108 STC1 , 109 and VCAM1 110 reinforcing an EndMT phenotype at the onset of angiogenic sprouting.…”

Cuproptosis-associated CDKN2A is targeted by plicamycin to regulate the microenvironment in patients with head and neck squamous cell carcinoma

“…Molecular dynamics simulation (MDS) is an important method for assessing the stability of complexes in an aqueous solution ( Hollingsworth and Dror, 2018 ; Hildebrand et al, 2019 ; Huang et al, 2022 ; Kang et al, 2022 ; Zhang et al, 2022 ). Stability of a system can be measured by the atomic root-mean-square deviation (RMSD).…”

Shared Proteins and Pathways of Cardiovascular and Cognitive Diseases: Relation to Vascular Cognitive Impairment

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