General Information of the Disease (ID: DIS00145)
Name
Myocardial injury
ICD
ICD-11: NB31
Full List of Target(s) of This Ferroptosis-centered Disease
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 LPS-induced myocardial injury [ICD-11: NB31]
Responsed Drug Pyridoxine Approved
Pathway Response Fatty acid metabolism hsa01212
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell proliferation
Cell apoptosis
In Vitro Model CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
Male c57BL/6 mice (8 weeks old) were purchased from Beijing Wei Tong Li Hua Experimental Animal Technology Co. Ltd. (Beijing, China). Mice were divided into control (n = 8), LPS (n = 9), and VitB6+LPS (n = 9) groups. Mice were pretreated with PBS or VitB6 for 6 h and then treated with LPS (4 mg/kg) for 24 h. Cardiac ultrasound was performed before sacrifice. Inhaled isoflurane was given to mice for volatile anesthesia and the chest hair was removed with a depilatory cream. Then, mice were fixed on the warmed imaging platform and wore with the coupling agent. The Vevo2100 imaging system, equipped with a 40-MHz high-frequency transducer (VisualSonics Inc., Toronto, Canada), was applied to perform non-invasive examinations. The M-mode echocardiogram at the parasternal long axis was used to obtain the ejection fraction (EF) of left ventricular and fractional shortening (FS).

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Response regulation Vitamin B6 (VitB6) is a water-soluble vitamin and includes pyridoxine, pyridoxal, pyridoxamine, and their phosphorylated forms. VitB6 regulated the expression of LPS-induced apoptosis-related proteins and iron regulatory proteins. It mediated the expression of Nrf2, transcription factor NF-E2-related factor 2, which promoted the expression of antioxidant enzymes and restrained LPS-induced ferroptosis and apoptosis. Overall, VitB6 can be used on novel therapies to relieve LPS-induced myocardial injury.
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 Obesity-induced cardiac injury [ICD-11: NB31]
Responsed Regulator hsa-miR-140-5p (miRNA) Driver
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
Six-week-old C57BL/6 male mice were randomly divided into two groups; the first group was fed a 45% high fat diet for 20 weeks while the control group were fed a normal chow diet. ATM-exosomes isolated from obese and lean mice were transferred into normal mice via tailvein injection(30 ug per week), as previously described. To investigate glutathione synthesis, 20 mM l-buthionine-(S,R)-sulfoximine (BSO) was added to the drinking water and administered to mice for 2 weeks. To inhibit ferroptosis, mice were given an intraperitoneal injection with Fer-1 (1 mg/kg).

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Response regulation Solute carrier family 7 member 11 (SLC7A11) is a downstream target of miR-140-5p, which induces ferroptosis via inhibition of GSH synthesis by targeting SLC7A11. Attenuating exosomal-miR-140-5p expression alleviates ferroptosis and obesity-induced cardiac injury by alleviating GSH inhibition.
References
Ref 1 Vitamin B6 Alleviates Lipopolysaccharide-induced Myocardial Injury by Ferroptosis and Apoptosis Regulation. Front Pharmacol. 2021 Dec 24;12:766820. doi: 10.3389/fphar.2021.766820. eCollection 2021.
Ref 2 Adipose tissue macrophage-derived exosomes induce ferroptosis via glutathione synthesis inhibition by targeting SLC7A11 in obesity-induced cardiac injury. Free Radic Biol Med. 2022 Mar;182:232-245. doi: 10.1016/j.freeradbiomed.2022.02.033. Epub 2022 Mar 7.