Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia

Cheng, Wanli; Lo, Huey‐Ming; Wang, Baowei; Chua, Su‐Kiat; Lu, Ming-Jen; Shyu, Kou‐Gi

doi:10.1016/j.jfma.2016.07.010

Cited by 15 publications

(14 citation statements)

References 33 publications

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“…TRIB3 is a stress-related gene that induces apoptosis during ER stress [46]. In the heart, TRIB3 has a low expression but is induced by hypoxia [47] or the transcription factor NF-kappaB, which it negatively regulates. In addition, TRIB3 sensitizes cells to TNF-and TRAIL-induced apoptosis and is involved in insulin signaling [48].…”

Section: Discussionmentioning

confidence: 99%

Analysis of De Novo Mutations in Sporadic Cardiomyopathies Emphasizes Their Clinical Relevance and Points to Novel Candidate Genes

Franaszczyk

Truszkowska

Chmielewski

et al. 2020

JCM

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The vast majority of cardiomyopathies have an autosomal dominant inheritance; hence, genetic testing is typically offered to patients with a positive family history. A de novo mutation is a new germline mutation not inherited from either parent. The purpose of our study was to search for de novo mutations in patients with cardiomyopathy and no evidence of the disease in the family. Using next-generation sequencing, we analyzed cardiomyopathy genes in 12 probands. In 8 (66.7%), we found de novo variants in known cardiomyopathy genes (TTN, DSP, SCN5A, TNNC1, TPM1, CRYAB, MYH7). In the remaining probands, the analysis was extended to whole exome sequencing in a trio (proband and parents). We found de novo variants in genes that, so far, were not associated with any disease (TRIB3, SLC2A6), a possible disease-causing biallelic genotype (APOBEC gene family), and a de novo mosaic variant without strong evidence of pathogenicity (UNC45A). The high prevalence of de novo mutations emphasizes that genetic screening is also indicated in cases of sporadic cardiomyopathy. Moreover, we have identified novel cardiomyopathy candidate genes that are likely to affect immunological function and/or reaction to stress that could be especially relevant in patients with disease onset associated with infection/infestation.

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Section: Discussionmentioning

confidence: 99%

Analysis of De Novo Mutations in Sporadic Cardiomyopathies Emphasizes Their Clinical Relevance and Points to Novel Candidate Genes

Franaszczyk

Truszkowska

Chmielewski

et al. 2020

JCM

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“…chen et al (28) reported a protective role of FGd5-aS1 in lipopolysaccharide-induced inflammatory injury in human periodontal ligament cells, as evidenced by counteraction of cell apoptosis and pro-inflammatory cytokine secretion via the nF-κB pathway. The role of FGD5-AS1 in inflammation in AMI requires further investigation, although ischemia-hypoxia is known to highly induce an inflammatory response in AMI (29).…”

Section: Discussionmentioning

confidence: 99%

lncRNA FGD5 antisense RNA 1 upregulates RORA to suppress hypoxic injury of human cardiomyocyte cells by inhibiting oxidative stress and apoptosis via miR‑195

et al. 2020

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FGd5 antisense rna 1 (FGd5-aS1) is a long non-coding rna in acute myocardial infarction (aMi), which is primarily caused by myocardial ischemia-hypoxia. retinoid acid receptor-related orphan receptor α (rora) is a key protector in maintaining heart function. However, the roles of FGd5-aS1 and rora in aMi have not previously been elucidated. The present study investigated the effect and mechanism of FGd5-aS1 and rora in human cardiomyocyte ac16 cells under hypoxia. reverse transcription-quantitative Pcr and western blotting demonstrated that FGd5-aS1 and rora were downregulated in the serum of patients with aMi and hypoxia-challenged ac16 cells. Functional experiments were performed via assays, flow cytometry and western blotting. in response to hypoxia, superoxide dismutase (Sod) activity was inhibited, but apoptosis rate and levels of reactive oxygen species and malondialdehyde were promoted in ac16 cells, accompanied by increased Bax and cleaved caspase-3 expression levels, and decreased Sod2 and glutathione peroxidase 1 expression levels. However, hypoxia-induced oxidative stress and apoptosis in ac16 cells were attenuated by ectopic expression of FGd5-aS1 or rora. Moreover, silencing rora counteracted the suppressive role of FGd5-aS1 overexpression in hypoxic injury. FGd5-aS1 controlled rora expression levels via microrna-195-5p (mir-195), as confirmed by dual-luciferase reporter and RNA pull-down assays. consistently, mir-195 knockdown suppressed hypoxia-induced oxidative stress and apoptosis in ac16 cells, which was abrogated by downregulating FGd5-aS1 or rora. in conclusion, FGd5-aS1 modulated hypoxic injury in human cardiomyocytes partially via the mir-195/rora axis, suggesting FGd5-aS1 as a potential target in interfering with the progression of aMi.

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“…Therefore, it is suggested that inhibition of apoptosis is an effective method to prevent myocardial infarction. Statins can reduce cardiomyocyte apoptosis by reducing the expression of TNF-α, and TRB3 in myocardial cells, inhibit ventricular remodeling after AMI, and improve cardiac function [4,[31][32] . In this study, the radioactive concentration signal of the 99m Tc-duramycin imaging in the statin treatment group was lower than that in the corresponding AMI group by visual analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Statins are hydroxymethylglutaric acid coenzyme reductase inhibitors, which have a significant lipid-lowering effect in the treatment of cardiovascular disease. Numerous studies showed that statins could effectively prevent apoptosis of myocardial cells in the infarcted area, reduce wall tension during diastole and reperfusion injury and myocardial ischemia, which may mechanistically attenuate myocardial apoptosis [2][3][4] . Therefore, it is pivotal that how to monitor myocardial cell death during myocardial infarction in vivo and evaluate the effects of statins and other anti-apoptotic drugs on myocardial infarction.…”

Section: Introductionmentioning

confidence: 99%

99m Tc-labeled Duramycin for detecting and monitoring cardiomyocyte death and assessing cardioprotection of atorvastatin in acute myocardial infarction

Tan

Abudupataer

Qiu

et al. 2020

Preprint

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Background: The objective of this study was to evaluate the feasibility of dynamic monitoring of myocardial cell death using 99m Tc-Duramycin single photon emission computed tomography/computed tomography (micro-SPECT/CT) imaging in a mouse model of acute myocardial infarction, and the anti-apoptosis effect of atorvastatin for cardio protection. Methods: Forty-five male Kunming mice were randomized into three groups: acute myocardial infarction (AMI) group, acute myocardial infarction with atorvastatin treatment (T-AMI) group, and the sham group. The mice of the AMI group and T-AMI group were subjected left coronary artery ligation. The T-AMI group was orally administered with atorvastatin 20 mg/ (kg day) 24 h before the surgery, the other two groups received only saline. Three groups of model mice were randomly selected at day 1 (D1), day 3 (D3), and day 7 (D7) day after surgery with 99m Tc-Duramycin micro-SPECT/CT imaging. Transthoracic echocardiography test was performed at D3 and D7 after surgery. The pathological evaluation, TUNEL assay and Western blot analysis were performed on heart specimens on D1, D3 and D7. Results: For up-taking of 99m Tc-duramycin in infarcted region, the mean value of semi-quantitative of AMI group were 2.62 on D1, 3.89 on D3 and 1.20 on D7. And for the T-AMI group, the mean value of semi-quantitative were 2.20 on D1, 2.97 on D3 and 1.30 on D7. The sham group had no positive imaging in myocardium, the mean value of semi-quantitative were 1.09, 1.14 and 1.10 on D1, D3 and D7, respectively. Meanwhile, 99m Tc-linear-duramycin imaging as control showed that there’s no radioactive uptake in the area of infarction region. But the T-AMI group imaging showed the tracer uptake decreased obviously compared to the uptake of AMI mice in infarcted region (L/N: 2.2 versus 2.62; 2.97 versus 3.89) on D3 and D7. LVEF was significantly reduced on D3 (42.67±2.51%) and D7 (27.71±2.52%) compared with the sham group (71.00±2.65%). The number of TUNEL positive cells decreased significantly on D3 (37.00±3.01 vs 51.00±3.61) and D7 (21.67±2.08 vs 27.65±2.51) post-MI after atorvastatin treatment. Additionally, the atorvastatin increased the expression level of anti-apoptotic protein BCL-2 and decreased the expression level of pro-apoptotic protein BAX. Conclusions: 99m Tc-Duramycin SPECT/CT imaging allowed to the non-invasively monitoring of myocardial cell death in a mouse model of acute myocardial infarction. Furthermore, this investigation and analysis could be used to assess and verify the anti-apoptosis effect of atorvastatin for cardio protection by in-vivo molecular imaging.

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Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia

Cited by 15 publications

References 33 publications

Analysis of De Novo Mutations in Sporadic Cardiomyopathies Emphasizes Their Clinical Relevance and Points to Novel Candidate Genes

Analysis of De Novo Mutations in Sporadic Cardiomyopathies Emphasizes Their Clinical Relevance and Points to Novel Candidate Genes

lncRNA FGD5 antisense RNA 1 upregulates RORA to suppress hypoxic injury of human cardiomyocyte cells by inhibiting oxidative stress and apoptosis via miR‑195

99m Tc-labeled Duramycin for detecting and monitoring cardiomyocyte death and assessing cardioprotection of atorvastatin in acute myocardial infarction

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