Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00093)
Name |
Acute myocardial infarction
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ICD |
ICD-11: BA41
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Full List of Target(s) of This Ferroptosis-centered Disease
Prostaglandin G/H synthase 2 (PTGS2)
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Marker | ||||
Responsed Disease | Coronary microembolization [ICD-11: BA41] | ||||
Responsed Drug | Atorvastatin | Investigative | |||
Responsed Regulator | Hypoxia-inducible factor 1-alpha (HIF1A) | Driver | |||
Pathway Response | Glutathione metabolism | hsa00480 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | mMTs (Mouse myocardial tissues) | ||||
In Vivo Model |
Rats were anesthetized intraperitoneally with 3% pentobarbital sodium (40 mg/kg). After mechanical ventilation, the rats were subjected to a thoracotomy to expose the hearts and ascending aorta. Finally, the ascending aorta was occluded for 10 s, and 8,000 polyester microspheres (diameter 42 um, Biosphere Medical, Rockland, MA, United States ) were injected into the left ventricle at the same time, while the sham-operated rats received the same dosage of normal saline instead. Forin vivotreatment, rats were treated with recombinant adeno-associated virus 9 (rAAV9)-GFP-shPtsg2 (Hanbio, Shanghai, China) or rAAV9-GFP-shHif1a (Genechem, Shanghai, China) at a dose of 1 x 1012 VG in 200 uL salineviaa single tail vein before CME. Deferoxamine (DFO) was purchased from Selleck (Shanghai, China) and administered intraperitoneally at a dose of 100 mg/kg for 7 days before CME. ATV (Pfizer, New York, United Kingdom) was administered intragastrically at a dose of 10 mg/kg for 7 days before CME.
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Response regulation | Ptgs2 was positively regulated by Hif1a and contributed to ferroptosis-dependent myocardial injury and inflammation. Furthermore, Atorvastatin protects against ferroptosis and inflammation induced by CME via the Hif1a/Ptgs2 pathway. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Marker | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | Gm47283 (IncRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
Male mice were used in this research. The mice were housed in a colony room at a controlled temperature (22) and humidity, under a 12-h light/dark cycle, and with food and water freely available. All surgical procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. In brief, the mice were anesthetized by 3% pentobarbital sodium and then ligated the anterior descending branch of the left coronary artery (LAD) for 48 h to establish the in vivo MI models. The sham group mice were opened the chest bur not ligated with LAD. The mice were randomly divided into three groups as follows: (1) the sham group, which underwent sham operation and received vehicle (PBS, caudal vein injection); (2) the model group, which was subjected to LAD and received vehicle (PBS, caudal vein injection); and (3) the siRNA group, which were subjected to LAD and treated with siRNA of lncRNA Gm47283 (30 nM siRNA dose per mice every day for one week, caudal vein injection).
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Response regulation | Stem cell membrane coated siRNA of lncRNA Gm47283 inhibits cardiomyocyte ferroptosis in myocardial infarction rat. Stem cell membrane-coated siRNA of lncRNA Gm47283 increases miR-706, and the miR-706 suppresses the expression of Ptgs2 to reduce lipid peroxidation toxicity, and then inhibits cardiomyocyte ferroptosis. Over-expression of lncRNA Gm47283 significantly increased the expression of Ptgs2 and Alox15 and repressed the expression of Gpx4. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Marker | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | mmu-miR-706 (miRNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
Male mice were used in this research. The mice were housed in a colony room at a controlled temperature (22) and humidity, under a 12-h light/dark cycle, and with food and water freely available. All surgical procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. In brief, the mice were anesthetized by 3% pentobarbital sodium and then ligated the anterior descending branch of the left coronary artery (LAD) for 48 h to establish the in vivo MI models. The sham group mice were opened the chest bur not ligated with LAD. The mice were randomly divided into three groups as follows: (1) the sham group, which underwent sham operation and received vehicle (PBS, caudal vein injection); (2) the model group, which was subjected to LAD and received vehicle (PBS, caudal vein injection); and (3) the siRNA group, which were subjected to LAD and treated with siRNA of lncRNA Gm47283 (30 nM siRNA dose per mice every day for one week, caudal vein injection).
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Response regulation | Stem cell membrane coated siRNA of lncRNA Gm47283 inhibits cardiomyocyte ferroptosis in myocardial infarction rat. Stem cell membrane-coated siRNA of lncRNA Gm47283 increases miR-706, and the miR-706 suppresses the expression of Ptgs2 to reduce lipid peroxidation toxicity, and then inhibits cardiomyocyte ferroptosis. Over-expression of lncRNA Gm47283 significantly increased the expression of Ptgs2 and Alox15 and repressed the expression of Gpx4. | ||||
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Drug | Fraxetin | Investigative | |||
Responsed Regulator | RAC-alpha serine/threonine-protein kinase (AKT1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS | |
In Vivo Model |
Male Wistar rats (200-250 g) were obtained from Slac Laboratory Animal Center (Shanghai, China) and kept in cages. The rats were anesthetized with 1% pentobarbital and then lied on its back. Thereafter, the left precordial area of the rats were shaved and disinfected, followed by trachea intubation for artificial ventilation. After the left thoracotomy, the heart was fully exposed and the left coronary artery (LAD) was ligated with a 6-0 prolene suture at 2-3 mm from its origin between the pulmonary artery conus and the left atrial appendage. After 30 min, the suture was gently removed to allow reperfusion for 2 h.
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Response regulation | Fraxetin activated phosphorylation of AKT and Nrf2 nuclear accumulation in Myocardial infarction in vivoandin vitromodels. Moreover, Fra reduced the activity of serum LDH, the accumulation of iron and the MDA level, and increased GSH and glutathione peroxidase 4 (GPX4) in rats with MI. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Drug | Iridin | Investigative | |||
Responsed Regulator | Fibronectin type III domain-containing protein 5 (FNDC5) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | hCMs (Human cardiomyocytes) | ||||
Response regulation | Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes. | ||||
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | |||
Target for Ferroptosis | Suppressor | |||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | |||
Responsed Drug | Iridin | Investigative | ||
Responsed Regulator | Fibronectin type III domain-containing protein 5 (FNDC5) | Suppressor | ||
Pathway Response | Ferroptosis | hsa04216 | ||
Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model | hCMs (Human cardiomyocytes) | |||
Response regulation | Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes. | |||
Solute carrier family 40 member 1 (SLC40A1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | Transcription regulator protein BACH1 (BACH1) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell metastasis | |||||
In Vitro Model | mEFs (Mouse embryonic fibroblasts) | ||||
In Vivo Model |
The generation of Bach1-/-mice on the C57BL/6J background was described previously. Mice 13 weeks of age were analyzed for models of AMI. The mice were subjected to ligation of the proximal LAD to induce AMI. They were randomly assigned to sham or AMI, DMSO, or DFX groups.
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Response regulation | BACH1 accelerates ferroptosis by suppressing labile iron metabolism. And ferritin genes (Fth1 and Ftl1) and the ferroportin gene (Slc40a1) were dramatically up-regulated in Bach1-/- MEFs. BACH1 controls the threshold of ferroptosis induction and may represent a therapeutic target for alleviating ferroptosis-related diseases, including myocardial infarction. | ||||
Polyunsaturated fatty acid lipoxygenase ALOX15 (ALOX15)
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | Gm47283 (IncRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
Male mice were used in this research. The mice were housed in a colony room at a controlled temperature (22) and humidity, under a 12-h light/dark cycle, and with food and water freely available. All surgical procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. In brief, the mice were anesthetized by 3% pentobarbital sodium and then ligated the anterior descending branch of the left coronary artery (LAD) for 48 h to establish the in vivo MI models. The sham group mice were opened the chest bur not ligated with LAD. The mice were randomly divided into three groups as follows: (1) the sham group, which underwent sham operation and received vehicle (PBS, caudal vein injection); (2) the model group, which was subjected to LAD and received vehicle (PBS, caudal vein injection); and (3) the siRNA group, which were subjected to LAD and treated with siRNA of lncRNA Gm47283 (30 nM siRNA dose per mice every day for one week, caudal vein injection).
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Response regulation | Stem cell membrane coated siRNA of lncRNA Gm47283 inhibits cardiomyocyte ferroptosis in myocardial infarction rat. Stem cell membrane-coated siRNA of lncRNA Gm47283 increases miR-706, and the miR-706 suppresses the expression of Ptgs2 to reduce lipid peroxidation toxicity, and then inhibits cardiomyocyte ferroptosis. Over-expression of lncRNA Gm47283 significantly increased the expression of Ptgs2 and Alox15 and repressed the expression of Gpx4. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | mmu-miR-706 (miRNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
Male mice were used in this research. The mice were housed in a colony room at a controlled temperature (22) and humidity, under a 12-h light/dark cycle, and with food and water freely available. All surgical procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. In brief, the mice were anesthetized by 3% pentobarbital sodium and then ligated the anterior descending branch of the left coronary artery (LAD) for 48 h to establish the in vivo MI models. The sham group mice were opened the chest bur not ligated with LAD. The mice were randomly divided into three groups as follows: (1) the sham group, which underwent sham operation and received vehicle (PBS, caudal vein injection); (2) the model group, which was subjected to LAD and received vehicle (PBS, caudal vein injection); and (3) the siRNA group, which were subjected to LAD and treated with siRNA of lncRNA Gm47283 (30 nM siRNA dose per mice every day for one week, caudal vein injection).
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Response regulation | Stem cell membrane coated siRNA of lncRNA Gm47283 inhibits cardiomyocyte ferroptosis in myocardial infarction rat. Stem cell membrane-coated siRNA of lncRNA Gm47283 increases miR-706, and the miR-706 suppresses the expression of Ptgs2 to reduce lipid peroxidation toxicity, and then inhibits cardiomyocyte ferroptosis. Over-expression of lncRNA Gm47283 significantly increased the expression of Ptgs2 and Alox15 and repressed the expression of Gpx4. | ||||
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [6] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Post-resuscitation myocardial dysfunction [ICD-11: BA41] | ||||
Responsed Drug | 4-(cyclohexylamino)-3-[(phenylmethyl)amino]-N-[2-(1-piperazinyl)ethyl]-benzenesulfonamide | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | rHTs (Rat hippocampal tissues) | ||||
In Vivo Model |
Male Sprague-Dawley rats (450 g-550 g) were purchased from Envigo (Frederick, Md). Animals were kept under standard conditions with a 12/12-h day/night cycle and received food and waterad libitum. Following induction with inhaling low flow CO2 for 30 s, animals were anesthetized by intraperitoneal injection of pentobarbital (45 mg/kg). Additional doses (10 mg/kg) were administered as needed based on tail pinch/withdrawal reflex to maintain anesthesia.
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Response regulation | Treatment with ferroptosis inhibitor, UAMC-3203 or/and DFO, reduced severity of myocardial dysfunction, and we further found that GPX4 and 4-HNE were significantly changed after CPR. Therefore, UAMC-3203 and DFO alleviated myocardial dysfunction via inhibiting ferroptosis, which could be a novel possible target for post-resuscitation myocardial dysfunction (PRMD) treatment. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Acute myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | mmu-miR-15a-5p (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
The male C57BL/6 mice (20-25 g, 10-week-old) were purchased from the Experimental Animal Center of Harbin Medical University (Harbin, China). Mice were anaesthetized with pentobarbital sodium (30 mg/kg, Sigma-Aldrich, St. Louis, USA) by intraperitoneal injection. The animals were fixed on the operating table in supine position, and the chest were sterilized and opened by blunt separation at the left 4th intercosal space. In the model group, the left anterior descending artery (LAD) was ligated with 7/0 silk suture for 3 days.
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Response regulation | GPX4 was the direct target of miR-15a-5p by luciferase reporter assay. Mechanistically, silencing transcription factor early growth response-1 (Egr-1) inhibited the level of miR-15a-5p, increased the protein expression of GPX4, accompanied by reduced ferroptosis and alleviated myocardial injury. These results provide a novel signaling pathway during the progression of acute myocardial infarction, namely Egr-1/miR-15a-5p/GPX4/ferroptosis. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Acute myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | Early growth response protein 1 (EGR1) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
The male C57BL/6 mice (20-25 g, 10-week-old) were purchased from the Experimental Animal Center of Harbin Medical University (Harbin, China). Mice were anaesthetized with pentobarbital sodium (30 mg/kg, Sigma-Aldrich, St. Louis, USA) by intraperitoneal injection. The animals were fixed on the operating table in supine position, and the chest were sterilized and opened by blunt separation at the left 4th intercosal space. In the model group, the left anterior descending artery (LAD) was ligated with 7/0 silk suture for 3 days.
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Response regulation | GPX4 was the direct target of miR-15a-5p by luciferase reporter assay. Mechanistically, silencing transcription factor early growth response-1 ( Egr-1) inhibited the level of miR-15a-5p, increased the protein expression of GPX4, accompanied by reduced ferroptosis and alleviated myocardial injury. These results provide a novel signaling pathway during the progression of acute myocardial infarction, namely Egr-1/miR-15a-5p/GPX4/ferroptosis. | ||||
Natural resistance-associated macrophage protein 2 (SLC11A2)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Acute myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | hsa-miR-23a-3p (miRNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | hUCB-MSCs (Human umbilical cord blood derived mesenchymal stem cells) | ||||
In Vivo Model |
A total of 72 C57BL/6J mice (six animals per group) were obtained from the Shanghai Laboratory Animals Center. The mouse model of AMI was performed by permanent ligation of the LAD coronary artery. PBS or exosomes (5 ug, in 20 ul PBS) was injected into the border zone of infarcted heart at three sites.
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Response regulation | The exosome of MSCs derived from human umbilical cord blood (HUCB-MSC) has been reported to have cardioprotective effects on mouse models of acute myocardial infarction (AMI) and cardiomyocyte hypoxia injury. HUCB-MSCs-exosomes may suppress DMT1 expression by miR-23a-3p to inhibit ferroptosis and attenuate myocardial injury. | ||||
Glutaminase liver isoform, mitochondrial (GLS2)
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [9] | |||
Target for Ferroptosis | Driver | |||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | |||
Responsed Regulator | hsa-miR-190a-5p (miRNA) | Suppressor | ||
Pathway Response | Glutathione metabolism | hsa00480 | ||
Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | |||
Cell proliferation | ||||
In Vitro Model | CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS |
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | |
Response regulation | MiR-190a-5p negatively regulate ferroptosis via directly targeting GLS2 in rat cardiomyocyte H9c2 cells. Forced expression of miR-190a-5p inhibited GLS2, resulting in downregulation of ROS, MDA and Fe2+accumulation. In summary, miR-190a-5p plays an essential role in regulation of ferroptosis of cardiomyocytes and suggest a potential therapeutic target for myocardial infarction. | |||
Ferritin light chain (FTL)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | Transcription regulator protein BACH1 (BACH1) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell metastasis | |||||
In Vitro Model | mEFs (Mouse embryonic fibroblasts) | ||||
In Vivo Model |
The generation of Bach1-/-mice on the C57BL/6J background was described previously. Mice 13 weeks of age were analyzed for models of AMI. The mice were subjected to ligation of the proximal LAD to induce AMI. They were randomly assigned to sham or AMI, DMSO, or DFX groups.
Click to Show/Hide
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Response regulation | BACH1 accelerates ferroptosis by suppressing labile iron metabolism. And ferritin genes (Fth1 and Ftl1) and the ferroportin gene (Slc40a1) were dramatically up-regulated in Bach1-/- MEFs. BACH1 controls the threshold of ferroptosis induction and may represent a therapeutic target for alleviating ferroptosis-related diseases, including myocardial infarction. | ||||
Ferritin heavy chain (FTH1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | Transcription regulator protein BACH1 (BACH1) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell metastasis | |||||
In Vitro Model | mEFs (Mouse embryonic fibroblasts) | ||||
In Vivo Model |
The generation of Bach1-/-mice on the C57BL/6J background was described previously. Mice 13 weeks of age were analyzed for models of AMI. The mice were subjected to ligation of the proximal LAD to induce AMI. They were randomly assigned to sham or AMI, DMSO, or DFX groups.
Click to Show/Hide
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Response regulation | BACH1 accelerates ferroptosis by suppressing labile iron metabolism. And ferritin genes (Fth1 and Ftl1) and the ferroportin gene (Slc40a1) were dramatically up-regulated in Bach1-/- MEFs. BACH1 controls the threshold of ferroptosis induction and may represent a therapeutic target for alleviating ferroptosis-related diseases, including myocardial infarction. | ||||
Unspecific Target
In total 6 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [10] | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Drug | Idebenone | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
mTOR signaling pathway | hsa04150 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS | |
In Vivo Model |
The mice were randomly divided into 3 groups as follows: sham + vehicle (5% DMSO + 10% PEG + 20% Tween80) group; MI + vehicle group; and MI + idebenone group. The 3 groups of mice then received vehicle or idebenone (100 mg/kg) in a final volume of 100 uL by intraperitoneal injections (Lee et al., 2021) 24 h and 2 h prior to surgery. A mouse model of MI was used as previously described (Guo et al., 2022b). In short, mice were placed under general anesthesia by intraperitoneal injection of pentobarbital, then endotracheal intubation and artificial respiration were performed. The left anterior descending coronary artery (LAD) of mice was ligated with a 6-0 silk suture, and the color of the LAD wall becoming pale confirmed the occlusion of the vessel. The same procedures were carried out on mice in the sham operation group, but with no LAD occlusion. The 3 groups of mice then received vehicle or idebenone (100 mg/kg/day) in a final volume of 100 uL by intraperitoneal injections once daily for 3 days.
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Response regulation | ROS-induced autophagy contributed to the consequent development of ferroptosisin vitro and in vivo. Idebenone alleviated ferroptosis by regulating excessive autophagy via the AMPK-mTOR pathway in myocardial infarction. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [11] | ||||
Responsed Disease | Acute myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | Aldo-keto reductase family 1 member C3 (AKR1C3) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | |
CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS | ||
Response regulation | AKR1C3 and HOXB4 are promising diagnostic biomarkers, providing novel insights into the ferroptosis mechanisms of acute myocardial infarction (AMI). | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [12] | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | CircRNA1615 (circRNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
C57BL/6J male mice of SPF grade, 8-10 weeks old, were used. The day before operation, the mice in the MI + ferrostatin-1 (Fer-1) group were injected a dose of 1 mg/kg ferroptosis inhibitor Fer-1 (SML0583-5MG, Sigma-Aldrich, USA). Fer-1 was dissolved in dimethyl sulfoxide (DMSO), then diluted in sterile saline. The sham group and the MI + NS group were injected with the same dose of saline (NS). The mice were anesthetized by 3% pentobarbital sodium via intraperitoneal injection, and the MI model was established by ligating the anterior descending branch of the left coronary artery (LAD) for 30 min.
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Response regulation | CircRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of myocardial infarction. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [11] | ||||
Responsed Disease | Acute myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | Homeobox protein Hox-B4 (HOXB4) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | |
CHO-S/H9C2 cells | Normal | Cricetulus griseus | CVCL_A0TS | ||
Response regulation | AKR1C3 and HOXB4 are promising diagnostic biomarkers, providing novel insights into the ferroptosis mechanisms of acute myocardial infarction (AMI). | ||||
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target | [12] | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | hsa-miR-152-3p (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
C57BL/6J male mice of SPF grade, 8-10 weeks old, were used. The day before operation, the mice in the MI + ferrostatin-1 (Fer-1) group were injected a dose of 1 mg/kg ferroptosis inhibitor Fer-1 (SML0583-5MG, Sigma-Aldrich, USA). Fer-1 was dissolved in dimethyl sulfoxide (DMSO), then diluted in sterile saline. The sham group and the MI + NS group were injected with the same dose of saline (NS). The mice were anesthetized by 3% pentobarbital sodium via intraperitoneal injection, and the MI model was established by ligating the anterior descending branch of the left coronary artery (LAD) for 30 min.
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Response regulation | CircRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of myocardial infarction. | ||||
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target | [12] | ||||
Responsed Disease | Myocardial infarction [ICD-11: BA41] | ||||
Responsed Regulator | Low-density lipoprotein receptor-related protein 6 (LRP6) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | HL-1 cells | Normal | Mus musculus | CVCL_0303 | |
In Vivo Model |
C57BL/6J male mice of SPF grade, 8-10 weeks old, were used. The day before operation, the mice in the MI + ferrostatin-1 (Fer-1) group were injected a dose of 1 mg/kg ferroptosis inhibitor Fer-1 (SML0583-5MG, Sigma-Aldrich, USA). Fer-1 was dissolved in dimethyl sulfoxide (DMSO), then diluted in sterile saline. The sham group and the MI + NS group were injected with the same dose of saline (NS). The mice were anesthetized by 3% pentobarbital sodium via intraperitoneal injection, and the MI model was established by ligating the anterior descending branch of the left coronary artery (LAD) for 30 min.
Click to Show/Hide
|
||||
Response regulation | CircRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of myocardial infarction. | ||||
References