Dataset Information

Targeting inflammation in atherosclerosis - from experimental insights to the clinic.

ABSTRACT: Atherosclerosis, a dominant and growing cause of death and disability worldwide, involves inflammation from its inception to the emergence of complications. Targeting inflammatory pathways could therefore provide a promising new avenue to prevent and treat atherosclerosis. Indeed, clinical studies have now demonstrated unequivocally that modulation of inflammation can forestall the clinical complications of atherosclerosis. This progress pinpoints the need for preclinical investigations to refine strategies for combatting inflammation in the human disease. In this Review, we consider a gamut of attractive possibilities for modifying inflammation in atherosclerosis, including targeting pivotal inflammatory pathways such as the inflammasomes, inhibiting cytokines, manipulating adaptive immunity and promoting pro-resolution mechanisms. Along with lifestyle measures, pharmacological interventions to mute inflammation could complement traditional targets, such as lipids and hypertension, to make new inroads into the management of atherosclerotic risk.

SUBMITTER: Soehnlein O

PROVIDER: S-EPMC8112476 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeting inflammation in atherosclerosis - from experimental insights to the clinic.

Soehnlein Oliver O Libby Peter P

Nature reviews. Drug discovery 20210511 8

Atherosclerosis, a dominant and growing cause of death and disability worldwide, involves inflammation from its inception to the emergence of complications. Targeting inflammatory pathways could therefore provide a promising new avenue to prevent and treat atherosclerosis. Indeed, clinical studies have now demonstrated unequivocally that modulation of inflammation can forestall the clinical complications of atherosclerosis. This progress pinpoints the need for preclinical investigations to refin ...[more]

PMID: 33976384

Similar Datasets

Project description:Atherosclerosis (AS) seriously affects human health. The role of microRNAs (miRNAs) in the pathogenesis and progression of AS has become a focus of research. Our goal was to identify the biological effect of differentially expressed miRNAs (DE-miRNAs) in AS. To analyze differentially expressed genes (DEGs), including differentially expressed mRNAs (DE-mRNAs) and DE-miRNAs, in AS by using the Gene Expression Omnibus (GEO) database and limma package. DEGs protein-protein interaction (PPI) network and functional enrichment analysis were constructed by using the search tool for the retrieval of interacting genes/proteins (STRING) database, Cytoscape software and Cytoscape plugin "ClueGO2.5.6". We established a coexpression network of dysregulated miRNAs and mRNAs to predict the function of miRNAs by using miRWalk database and Pearson correlation coefficient (PCC) analysis. Cellular experiments were used to validate the results of bioinformatics. First, 69 common DEGs were obtained from datasets GSE43292 and GSE97210 using the limma package in R. Next, a DEG PPI network was constructed. Functional enrichment analysis of DEGs showed that 11 functional pathways were significantly enriched, such as positive regulation of monocyte chemotaxis. Seven common DE-miRNAs were obtained from the GSE99685 dataset and DE-mRNAs predicted miRNAs through the miRWalk database. The miRNA-mRNA network constructed using Cytoscape software suggested that miR-148a-3p targeted contactin 4 (CNTN4). Quantitative real-time polymerase chain reaction (qRT-PCR) assay results indicated that miR-148a-3p was downregulated and CNTN4 was upregulated in the THP-1 + phorbol 12-myristate 13-acetate (PMA) + oxidized low-density lipoprotein (oxLDL) group compared with the THP-1 + PMA group. qRT-PCR, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) found that upregulated miR-148a-3p significantly inhibited the expression of CNTN4, cell apoptosis, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations in oxLDL-induced THP-1 macrophages. In addition, a dual-luciferase reporter assay demonstrated that CNTN4 was a target gene of miR-148a-3p. Overall, these findings suggested that miR-148a-3p inhibited oxLDL-induced cell apoptosis and inflammation via targeting CNTN4 in THP-1 macrophages.

Dataset Information

Targeting inflammation in atherosclerosis - from experimental insights to the clinic.

Publications

Targeting inflammation in atherosclerosis - from experimental insights to the clinic.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets