Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00096)
Name |
Supraventricular tachycardia
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ICD |
ICD-11: BC81
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Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Atrial fibrillation [ICD-11: BC81.3] | ||||
Responsed Drug | Icariin | Phase 3 | |||
Responsed Regulator | NAD-dependent protein deacetylase sirtuin-1 (SIRT1) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
Adult male mice (C57BL6) aged 12 weeks were purchased from HUAFUKANG Bioscience Co, Ltd (Beijing, China) and housed in controlled temperature with free access to water and standard pellet chow. The animal studies were approved by the General Hospital of Northern Theatre Command Animal Care Committee. All experiments were carried out in accordance with institutional regulations and in adherence with the Guide for the Care and Use of Laboratory Animals issued by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Additionally, the study was reported in accordance with ARRIVE guidelines. After an accommodation period of 7 days, the mice were randomly assigned into the following groups (n = 18/group): control group, control + Ferrostatin-1 (Fer-1)/Erastin/EX527 group, ethanol (EtOH) group, EtOH + Fer-1 group, EtOH + Icar group, EtOH + Icar + Erastin group, EtOH + Icar + EX527 group.
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Response regulation | Icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to atrial fibrillation. | ||||
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Atrial fibrillation [ICD-11: BC81.3] | ||||
Responsed Drug | Icariin | Phase 3 | |||
Responsed Regulator | NAD-dependent protein deacetylase sirtuin-1 (SIRT1) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
Adult male mice (C57BL6) aged 12 weeks were purchased from HUAFUKANG Bioscience Co, Ltd (Beijing, China) and housed in controlled temperature with free access to water and standard pellet chow. The animal studies were approved by the General Hospital of Northern Theatre Command Animal Care Committee. All experiments were carried out in accordance with institutional regulations and in adherence with the Guide for the Care and Use of Laboratory Animals issued by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Additionally, the study was reported in accordance with ARRIVE guidelines. After an accommodation period of 7 days, the mice were randomly assigned into the following groups (n = 18/group): control group, control + Ferrostatin-1 (Fer-1)/Erastin/EX527 group, ethanol (EtOH) group, EtOH + Fer-1 group, EtOH + Icar group, EtOH + Icar + Erastin group, EtOH + Icar + EX527 group.
Click to Show/Hide
|
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Response regulation | Icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to atrial fibrillation. | ||||
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Atrial fibrillation [ICD-11: BC81.3] | ||||
Responsed Drug | Icariin | Phase 3 | |||
Responsed Regulator | NAD-dependent protein deacetylase sirtuin-1 (SIRT1) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
Adult male mice (C57BL6) aged 12 weeks were purchased from HUAFUKANG Bioscience Co, Ltd (Beijing, China) and housed in controlled temperature with free access to water and standard pellet chow. The animal studies were approved by the General Hospital of Northern Theatre Command Animal Care Committee. All experiments were carried out in accordance with institutional regulations and in adherence with the Guide for the Care and Use of Laboratory Animals issued by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Additionally, the study was reported in accordance with ARRIVE guidelines. After an accommodation period of 7 days, the mice were randomly assigned into the following groups (n = 18/group): control group, control + Ferrostatin-1 (Fer-1)/Erastin/EX527 group, ethanol (EtOH) group, EtOH + Fer-1 group, EtOH + Icar group, EtOH + Icar + Erastin group, EtOH + Icar + EX527 group.
Click to Show/Hide
|
||||
Response regulation | Icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to atrial fibrillation. | ||||
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Atrial fibrillation [ICD-11: BC81.3] | ||||
Responsed Drug | Icariin | Phase 3 | |||
Responsed Regulator | NAD-dependent protein deacetylase sirtuin-1 (SIRT1) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
Adult male mice (C57BL6) aged 12 weeks were purchased from HUAFUKANG Bioscience Co, Ltd (Beijing, China) and housed in controlled temperature with free access to water and standard pellet chow. The animal studies were approved by the General Hospital of Northern Theatre Command Animal Care Committee. All experiments were carried out in accordance with institutional regulations and in adherence with the Guide for the Care and Use of Laboratory Animals issued by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Additionally, the study was reported in accordance with ARRIVE guidelines. After an accommodation period of 7 days, the mice were randomly assigned into the following groups (n = 18/group): control group, control + Ferrostatin-1 (Fer-1)/Erastin/EX527 group, ethanol (EtOH) group, EtOH + Fer-1 group, EtOH + Icar group, EtOH + Icar + Erastin group, EtOH + Icar + EX527 group.
Click to Show/Hide
|
||||
Response regulation | Icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to atrial fibrillation. | ||||
Cystine/glutamate transporter (SLC7A11)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Atrial fibrillation [ICD-11: BC81.3] | ||||
Responsed Drug | GW4869 | Investigative | |||
Responsed Regulator | rno-miR-23a-3p (miRNA) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS | |
rCFs (Rat cardiac fibroblasts) | |||||
In Vivo Model |
Eighteen beagles, randomly divided into three groups, both sexes and an average age of 1 year, weighing 7.5 ± 1.5 kg, were used for the study as follows: Sham group (n = 6), Pacing group (n = 6), and GW4869 + Pacing group (n = 6). Each beagle canine was given an intramuscular injection of 25 mg/kg ketamine sulfate before being premedicated with pentobarbital sodium (30 mg/kg, intravenous injection) and ventilated with room air by a respirator (MAO01746, Harvard Apparatus Holliston, United States). Venous access was established to supply saline (50-100 mL/h) or pentobarbital sodium (2.5 mg/kg/h).
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Response regulation | The exosome inhibitor GW4869 reduced ferroptosis, fibrosis, and inflammation and improved histological and electrophysiological remodeling. Pacing-CF-exos highly expressed miR-23a-3p by informatics analysis and experimental verification. Inhibitor- miR-23a-3p protected h9c2 cells from ferroptosis accompanying with upregulation of SLC7A11. The development of atrial fibrillation (AF) in a persistent direction could be prevented by intervening with exosomal miRNAs to reduce oxidative stress injury and ferroptosis. | ||||
References