Potential Therapeutic Effect of All-Trans Retinoic Acid on Atherosclerosis

Deng, Qile; Chen, Jixiang

doi:10.3390/biom12070869

Cited by 11 publications

(2 citation statements)

References 141 publications

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“…Tretinoin plays a potential role in the prevention of CVDs, and studies have shown that it can influence the development of AS by regulating various biological processes in immune cells, such as cell proliferation, migration, and phenotypic transformation. It is also involved in the regulation of blood glucose concentration, lipid metabolism, and the inflammatory response, thereby improving AS 110 . In a study, serum tretinoin concentrations were found to be significantly lower in NASH patients than in healthy subjects 111 .…”

Section: Discussionmentioning

confidence: 99%

CXCL9, IL2RB, and SPP1, potential diagnostic biomarkers in the co-morbidity pattern of atherosclerosis and non-alcoholic steatohepatitis

Wu,

Yuan,

Pan

et al. 2024

Sci Rep

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Non-alcoholic steatohepatitis (NASH) is a hepatocyte inflammation based on hepatocellular steatosis, yet there is no effective drug treatment. Atherosclerosis (AS) is caused by lipid deposition in the endothelium, which can lead to various cardiovascular diseases. NASH and AS share common risk factors, and NASH can also elevate the risk of AS, causing a higher morbidity and mortality rate for atherosclerotic heart disease. Therefore, timely detection and diagnosis of NASH and AS are particularly important. In this study, differential gene expression analysis and weighted gene co-expression network analysis were performed on the AS (GSE100927) and NASH (GSE89632) datasets to obtain common crosstalk genes, respectively. Then, candidate Hub genes were screened using four topological algorithms and externally validated in the GSE43292 and GSE63067 datasets to obtain Hub genes. Furthermore, immune infiltration analysis and gene set variation analysis were performed on the Hub genes to explore the underlying mechanisms. The DGIbd database was used to screen candidate drugs for AS and NASH. Finally, a NASH model was constructed using free fatty acid-induced human L02 cells, an AS model was constructed using lipopolysaccharide-induced HUVECs, and a co-morbidity model was constructed using L02 cells and HUVECs to verify Hub gene expression. The result showed that a total of 113 genes common to both AS and NASH were identified as crosstalk genes, and enrichment analysis indicated that these genes were mainly involved in the regulation of immune and metabolism-related pathways. 28 candidate Hub genes were screened according to four topological algorithms, and CXCL9, IL2RB, and SPP1 were identified as Hub genes after in vitro experiments and external dataset validation. The ROC curves and SVM modeling demonstrated the good diagnostic efficacy of these three Hub genes. In addition, the Hub genes are strongly associated with immune cell infiltration, especially macrophages and γ–δ T cell infiltration. Finally, five potential therapeutic drugs were identified. has-miR-185 and hsa-miR-335 were closely related to AS and NASH. This study demonstrates that CXCL9, IL2RB, and SPP1 may serve as potential biomarkers for the diagnosis of the co-morbidity patterns of AS and NASH and as potential targets for drug therapy.

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Section: Discussionmentioning

confidence: 99%

CXCL9, IL2RB, and SPP1, potential diagnostic biomarkers in the co-morbidity pattern of atherosclerosis and non-alcoholic steatohepatitis

Wu,

Yuan,

Pan

et al. 2024

Sci Rep

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“…Unlike psoriasis, atherosclerosis treatment focuses on limiting cholesterol accumulation and reducing clotting risk. ATRA's efficacy in treating atherosclerosis is currently under investigation [59]. However, its anti-inflammatory effect on mediators of atherosclerosis, such as macrophages and Tregs, highlights a possibility to reduce disease progression [58,59].…”

Section: Atra Downregulation Of Inflammatory Disease Processesmentioning

confidence: 99%

Retinoic Acid Induced Cell Signaling as a Counter Against Disease

Franco,

Pan

2023

J Cell Signal

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Many disease processes result from disruption of physiologic cell signaling pathways. Cancer often develops from the loss of cell cycle regulation, while inflammatory disease results from dysregulated immune activity. Likewise, many microbial infections avoid immune clearance by interfering with cellular antimicrobial pathways. Retinoic Acid (RA) is a dynamic compound, derived from vitamin A, that can regulate various signaling pathways. RA induced cell signaling has proven beneficial against different diseases, such as Acute Promyelocytic Leukemia (APL) and psoriasis. Against APL, RA induces cellular differentiation in cancer cells to restore proper function. In psoriasis, RA downregulates inflammatory pathways, such as NF-κB. RA’s anti-inflammatory properties have also been examined in the context of sepsis, where recent animal studies have shown positive benefits. Along with regulating inflammation, RA exhibits indirect antimicrobial properties. Unlike conventional antimicrobials which target pathogens directly, RA functions as a host-directed therapy (HDT), promoting cell antimicrobial defenses. Recent studies examining RA have shown that it can improve macrophage clearance of microbial pathogens and stimulate the antiviral type-I interferon (IFN) response. RA’s effectiveness has been demonstrated against clinically relevant pathogens, such as Mycobacterium tuberculosis, Aspergillus fumigatus, and Measles virus. In this review, the therapeutic potential of RA to treat various diseases by regulating cell signaling pathways will be explored.

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