Guanxin V alleviates acute myocardial infarction by restraining oxidative stress damage, apoptosis, and fibrosis through the TGF-β1 signalling pathway

Liang, Bo; Zhang, Xiaoxiao; Li, Rui; Zhu, Yong-Chun; Tian, Xiao-Jie; Gu, Ning

doi:10.1016/j.phymed.2022.154077

Cited by 28 publications

(13 citation statements)

References 34 publications

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“…Oxidative stress is the main cause of the poor prognosis of ischemic myocardial injury in AMI [17]. Several other studies have also identified oxidative stress as a key factor in AMI [18][19][20]. Therefore, therapy that targets inflammation and oxidative stress may become a potential treatment strategy for patients with AMI.…”

Section: Introductionmentioning

confidence: 99%

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

Xie

Luo

et al. 2022

Oxidative Medicine and Cellular Longevity

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Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases with high morbidity and mortality. Numerous studies have indicated that S100A12 may has an essential role in the occurrence and development of AMI, and in-depth studies are currently lacking. The purpose of this study is to investigate the effect of S100A12 on inflammation and oxidative stress and to determine its clinical applicability in AMI. Here, AMI datasets used to explore the expression pattern of S100A12 in AMI were derived from the Gene Expression Omnibus (GEO) database. The pooled standard average deviation (SMD) was calculated to further determine S100A12 expression. The overlapping differentially expressed genes (DEGs) contained in all included datasets were recognized by the GEO2R tool. Then, functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were carried out to determine the molecular function of overlapping DEGs. Gene set enrichment analysis (GSEA) was conducted to determine unrevealed mechanisms of S100A12. Summary receiver operating characteristic (SROC) curve analysis and receiver operating characteristic (ROC) curve analysis were carried out to identify the diagnostic capabilities of S100A12. Moreover, we screened miRNAs targeting S100A12 using three online databases (miRWalk, TargetScan, and miRDB). In addition, by comprehensively using enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR (RT–qPCR), Western blotting (WB) methods, etc., we used the AC16 cells to validate the expression and underlying mechanism of S100A12. In our study, five datasets related to AMI, GSE24519, GSE60993, GSE66360, GSE97320, and GSE48060 were included; 412 overlapping DEGs were identified. Protein-protein interaction (PPI) network and functional analyses showed that S100A12 was a pivotal gene related to inflammation and oxidative stress. Then, S100A12 overexpression was identified based on the included datasets. The pooled standard average deviation (SMD) also showed that S100A12 was upregulated in AMI ( SMD = 1.36 , 95% CI: 0.70-2.03, p = 0.024 ). The SROC curve analysis result suggested that S100A12 had remarkable diagnostic ability in AMI ( AUC = 0.90 , 95% CI: 0.87-0.92). And nine miRNAs targeting S100A12 were also identified. Additionally, the overexpression of S100A12 was further confirmed that it maybe promote inflammation and oxidative stress in AMI through comprehensive in vitro experiments. In summary, our study suggests that overexpressed S100A12 may be a latent diagnostic biomarker and therapeutic target of AMI that induces excessive inflammation and oxidative stress. Nine miRNAs targeting S100A12 may play a crucial role in AMI, but further studies are still needed. Our work provides a positive inspiration for the in-depth study of S100A12 in AMI.

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Section: Introductionmentioning

confidence: 99%

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

Xie

Luo

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Hypoxia secondary to CNI can induce the persistent upregulation of TGF-β1, and increased TGF-β1 is widely acknowledged as a central hallmark of CNI-ED [6-8]. Apart from pro-brotic effects, numerous investigations have documented that excessive activation of TGF-β1 and its associated pathways, can trigger apoptosis and oxidative stress-related damage [17,[45][46][47][48][49][50]. Exogenous TGF-β1 had been shown to promote apoptosis and ROS generation in CCSMCs by activating Smad signaling and antagonizing PI3K/AKT signaling [9].…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 scaffolding domain-derived peptide enhances the antiapoptotic progresses of corpus cavernosum smooth muscle cells after cavernous nerve injury

Xi,

Xia,

Feng

et al. 2023

Preprint

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Increased apoptosis in penis due to cavernous nerve injury (CNI) is a crucial contributor to erectile dysfunction (ED). Caveolin-1 scaffolding domain (CSD)-derived peptide (CSD peptide) has been found to exhibit potential antiapoptotic property. However, it remains unknown whether CSD peptide therapy can alleviate the apoptosis of corpus cavernosum smooth muscle cells (CCSMCs), and ED in CNI rats. We aimed to validate the assumption that CSD peptide may promote the improvement of bilateral CNI-induced ED (BCNI-ED) by enhancing the antiapoptotic processses of CCSMCs. Fifteen 10-week-old male Sprague-Dawley (SD) rats were assigned into three groups at random: sham surgery (Sham) group and BCNI groups that underwent saline or CSD peptide treatment respectively. At 3 weeks postoperatively, erectile function (EF) was assessed. Then, processed penis was histologically examined. To investigate the mechanism of action of CSD peptide in treating BCNI-ED, an in vitro model of CCSMC apoptosis was established using transforming growth factor-beta 1 (TGF-β1). In BCNI rats, CSD peptide significantly prevented ED, raised the phosphorylation of AKT, and decreased the expressions of Bax/Bcl-2 ratio, caspase3, and the quantity of apoptotic cells. TGF-β1-treated CCSMCs exhibited lower levels of p-AKT, mitochondrial membrane potential (MMP), superoxide dismutase (SOD), and cell viability, along with higher levels of Bax/Bcl-2 ratio, apoptotic index, reactive oxygen species (ROS), and malondialdehyde (MDA). However, CSD peptide partially restored these alterations. Consequently, BCNI-ED may be prevented in part by CSD peptide-mediated reduction of CCSMC apoptosis, which further promotes the development of CSD peptide as an effective therapy for pRP-ED.

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“…Further studies are needed to characterize the effect of 16α-OHE1 on myocardial structure. It has been noted that pathological cardiac remodeling is characterized by cardiac hypertrophy and brosis, which are pathological features of many heart diseases and can induce severe myocardial damage [28,29] .…”

Section: Discussionmentioning

confidence: 99%

A Novel Mechanism of 16α-OHE1, One of Estrogen Metabolites, Alleviating Inflammatory Infiltration in Hypoxia-Induced Myocardial Injury via β2-Adrenergic Receptor

Zhou

Yin

Cui

et al. 2023

Preprint

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Objective The study aimed to investigate the protective effect of 16α-OHE1 on myocardial injury caused by hypoxia.Methods and results Rats were exposed to normoxia or hypoxia conditions simulating an high altitude of 6000 m in a low-pressure chamber for 7 days. Post-exposure, evaluations were made on cardiac function, myocardial enzyme concentrations, histopathological modifications, inflammatory infiltration, and β2-adrenergic receptor (β2AR) expression levels. In parallel, H9C2 cells were cultured under standard oxygen conditions or in a three-gas incubator containing 5% O2 for 24 h. Cell viability, apoptosis, inflammatory infiltration, and myocardial enzyme levels in H9C2 cells were measured. Hypoxia induced significant myocardial damage, marked by impaired cardiac function, myocardial structural changes, inflammatory infiltration, and increased apoptosis. Pre-treatment with 16α-OHE1 significantly improved heart function and reduced myocardial enzyme release. The increased inflammatory response was also significantly suppressed. In addition to preserving myocardial structures, hypoxia-induced apoptosis in cardiomyocytes was significantly weakened. Notably, these protective effects of 16α-OHE1 were linked with the upregulation of β2AR expression. However, when β2AR was inhibited by ICI 118,551, the protective effect of 16α-OHE1 on the myocardium was abrogated.Conclusion 16α-OHE1 could reduce hypoxia-induced myocardial injury in rats through β2-adrenoceptors.

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Guanxin V alleviates acute myocardial infarction by restraining oxidative stress damage, apoptosis, and fibrosis through the TGF-β1 signalling pathway

Cited by 28 publications

References 34 publications

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

Caveolin-1 scaffolding domain-derived peptide enhances the antiapoptotic progresses of corpus cavernosum smooth muscle cells after cavernous nerve injury

A Novel Mechanism of 16α-OHE1, One of Estrogen Metabolites, Alleviating Inflammatory Infiltration in Hypoxia-Induced Myocardial Injury via β2-Adrenergic Receptor

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