Tumor Protein p53 Gene and Cardiovascular Disease

Tzovaras, Alexandros; Gentimi, Fotini; Nikolaou, Michail

doi:10.1177/0003319718772412

Cited by 7 publications

(5 citation statements)

References 10 publications

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“…Regulating the expression of TP53 protein can promote the repair process of heart endothelial cells and help vascular remodeling to reduce cardiovascular damage [29]. In our study, the protective effect of TP53 on cardiomyocytes was not significant, but its trend was obvious.…”

Section: Discussioncontrasting

confidence: 53%

Network Pharmacology Analysis and Experimental Verification Strategies Reveal the Action Mechanism of Danshen Decoction in Treating Ischemic Cardiomyopathy

Liu

Yuan

Luo

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Danshen Decoction comprises Salvia miltiorrhiza, Santalum album, and Amomum villosum. It can promote blood circulation and remove blood stasis, and is commonly used in the treatment of gastric and duodenal ulcers, coronary heart disease, angina pectoris, etc. This research is based on network pharmacology and is experimentally verified to explore the potential mechanism of Danshen Decoction in the treatment of ischemic cardiomyopathy (ICM). Methods. The effective components and targets of Danshen Decoction were firstly extracted from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, the drug-component-target-disease network was then constructed, the protein-protein interaction (PPI) network was constructed, the Gene Ontology (GO) enrichment analysis was carried out, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed in order to find the potential active components and therapeutic mechanisms. Finally, the in vitro hypoxia/reoxygenation model in H9c2 cells was established to verify the predicted active components and therapeutic mechanisms. Results. The results showed that Danshen Decoction has 67 potential active components and 109 therapeutic targets in treating ICM. These targets were rich in a variety of gene functions and different signaling pathways; the main gene targets include TP53, c-Jun, and Akt1. Go enrichment analysis showed that response to drug, membrane raft, and G protein-coupled amine receiver activity rank first in each process, and the main signaling pathways include PI3K-Akt signaling pathway. Through molecular docking and experimental verification of the major active components and core therapeutic targets, the active components of Danshen Decoction demonstrated an ability to reduce the cell damage caused by hypoxia/reoxygenation in H9c2 cells by regulating the core therapeutic target including Akt1, c-Jun, and TP53. Conclusion. Danshen Decoction has the effect of treating ICM in multiple ways, which is consistent with the results of network pharmacology. This laid a foundation for further study in exploring the active principles and pharmacological mechanism of Danshen Decoction.

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Section: Discussioncontrasting

confidence: 53%

Network Pharmacology Analysis and Experimental Verification Strategies Reveal the Action Mechanism of Danshen Decoction in Treating Ischemic Cardiomyopathy

Liu

Yuan

Luo

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Further studies have shown that wild-type p53 gene can promote the release of cytochrome C and other apoptosis inducing factors by affecting cell cycle and the change of mitochondrial Bcl-2/Bax ratio, start Caspase protease-cascaded reaction and activate the occurrence of myocardial cell apoptosis, so as to promote the apoptosis of cardiovascular system, and play an omportant role in the pathogenesis of myocardial infarction, heart failure, atherosclerosis and other cardiovascular diseases ( 128 ). Currentlly, different types of p53 genes are used as targets for the therapeutic strategy of cardiovascular diseases ( 129 ). Many discoveries also have indicated that autophagy inhibits p53 and p53 activates autophagy ( 130 ).…”

Section: Role Of Cascade Autophagy In Cardiovascular Disease Through ...mentioning

confidence: 99%

The role of autophagy in cardiovascular disease: Cross-interference of signaling pathways and underlying therapeutic targets

Jiang

Zhou

Yang

et al. 2023

Front. Cardiovasc. Med.

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Autophagy is a conserved lysosomal pathway for the degradation of cytoplasmic proteins and organelles, which realizes the metabolic needs of cells and the renewal of organelles. Autophagy-related genes (ATGs) are the main molecular mechanisms controlling autophagy, and their functions can coordinate the whole autophagic process. Autophagy can also play a role in cardiovascular disease through several key signaling pathways, including PI3K/Akt/mTOR, IGF/EGF, AMPK/mTOR, MAPKs, p53, Nrf2/p62, Wnt/β-catenin and NF-κB pathways. In this paper, we reviewed the signaling pathway of cross-interference between autophagy and cardiovascular diseases, and analyzed the development status of novel cardiovascular disease treatment by targeting the core molecular mechanism of autophagy as well as the critical signaling pathway. Induction or inhibition of autophagy through molecular mechanisms and signaling pathways can provide therapeutic benefits for patients. Meanwhile, we hope to provide a unique insight into cardiovascular treatment strategies by understanding the molecular mechanism and signaling pathway of crosstalk between autophagy and cardiovascular diseases.

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“…The p53 factor can induce SMC apoptosis in vitro and inhibit SMC proliferation in vitro and in vivo . It is accumulated in atherosclerotic lesions, and its ability to initiate apoptosis in these lesions may depend on interaction with MDM2 protein, a regulator of p53 stability [ 81 – 84 ]. It was reported [ 85 ] that the cytomegalovirus gene counteracts p53-induced apoptosis of SMCs.…”

Section: Apoptosis Markersmentioning

confidence: 99%

Apoptosis and Cell Proliferation Markers in Inflammatory-Fibroproliferative Diseases of the Vessel Wall (Review)

et al. 2020

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Apoptosis is the main feature of inflammatory-fibroproliferative disorders of the vessel wall. Studies in animal models have shown that smooth muscle cells (SMCs) cultured from endarterectomy specimens from the affected area proliferate more slowly and display higher apoptotic indices than SMCs derived from the normal vessel wall. Apoptotic cells were found in the destabilized atherosclerotic plaques, as well as in the samples with restenosis of the reconstruction area. Injury to the vessel wall causes two waves of apoptosis. The first wave is the rapid apoptosis in the media that occurs within a few hours after injury and leads to a marked reduction in the number of vascular wall cells. The second wave of apoptosis occurs much later (from several days to weeks) and is limited by the SMCs within the developing neointima. Up to 14% of the neointimal SMCs undergo apoptosis 20 days after balloon angioplasty. Ligation of the external carotid artery in a rabbit model led to a marked decrease in blood flow in the common carotid artery, which correlated with the increased apoptosis of endothelial cells and SMCs. Angioplasty-induced death of SMCs is regulated by a redox-sensitive signaling pathway, and topical administration of antioxidants can minimize vascular cell loss. On the whole, studies show that apoptosis is prevalent in vascular lesions, controlling the viability of both inflammatory and vascular cells, determining the cellular composition of the vessel wall. The main markers of apoptosis (Fas, Fas ligand, p53, Bcl-2, Bax) and cell proliferation (toll receptor) have been considered in the current review.

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Tumor Protein p53 Gene and Cardiovascular Disease

Cited by 7 publications

References 10 publications

Network Pharmacology Analysis and Experimental Verification Strategies Reveal the Action Mechanism of Danshen Decoction in Treating Ischemic Cardiomyopathy

Network Pharmacology Analysis and Experimental Verification Strategies Reveal the Action Mechanism of Danshen Decoction in Treating Ischemic Cardiomyopathy

The role of autophagy in cardiovascular disease: Cross-interference of signaling pathways and underlying therapeutic targets

Apoptosis and Cell Proliferation Markers in Inflammatory-Fibroproliferative Diseases of the Vessel Wall (Review)

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