Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00100)
Name
Atherosclerosis
ICD
ICD-11: BD40
Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Atherosclerosis [ICD-11: BD40]
Responsed Drug Ferric ammonium citrate Investigative
 Drug Info 
Responsed Regulator NAD-dependent protein deacetylase sirtuin-1 (SIRT1) Suppressor
 Regulator Info 
Pathway Response Autophagy hsa04140
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In Vivo Model
A total of 20 male Apoe-/-mice (6-8 weeks of age, 18-22 g) were purchased from Charles River (Beijing, China). Mice were randomly assigned to a control group (normal diet: 4% fat, cholesterol free, and sodium cholate) and an AS group (high-fat diet: 20% fat, 1.25% cholesterol, and 0.5% sodium cholate).

    Click to Show/Hide
Response regulation Ferric ammonium citrate(FAC) can induce a decrease in foam cell activity rather than macrophage activity, increase lipid ROS levels, decrease GPX4 expression and inhibit SIRT1 expression. Activation of SIRT1 can inhibit the ferroptosis and IL-1 and IL-18 levels of foam cells in excess iron by autophagy, providing a novel therapeutic target for atherosclerosis(AS).
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Atherosclerosis [ICD-11: BD40]
Responsed Regulator hsa-mir-132 (Precursor RNA) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HUVECs (Human umbilical vein endothelial cells)
Response regulation MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis, which may serve as a promising therapeutic target for atherosclerosis. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs (P < 0.001).
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Atherosclerosis [ICD-11: BD40]
Responsed Regulator All trans-polyprenyl-diphosphate synthase PDSS2 (PDSS2) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model hCAECs (Human coronary artery endothelial cells)
In Vivo Model
Eight-week-old male mice PDSS2 wild type [WT (n = 6)], PDSS2/, Nrf2/, Nrf2+/+, on C57BL/6 background (18-22 g) were provided by Nanjing Medical University (Nanjing, China). PDSS2/ mice (n = 12) were crossed with PDSS2/ to obtain PDSS2/, Nrf2/ (n = 6) and PDSS2/, Nrf2+/+ (n = 6) mice. Mice were fed an AIN76A Western diet for 8 weeks to accelerate the development of AS. Mice from each group were euthanized after 8 weeks.

    Click to Show/Hide
Response regulation Overexpression of PDSS2 suppressed the ferroptosis of HCAECs by promoting the activation of Nrf2 pathways. Thence PDSS2 may play a cardio-protective role in atherosclerosis (AS).
NADPH oxidase 4 (NOX4)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Atherosclerosis [ICD-11: BD40]
Responsed Regulator hsa-mir-132 (Precursor RNA) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HUVECs (Human umbilical vein endothelial cells)
Response regulation MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis, which may serve as a promising therapeutic target for atherosclerosis. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs (P < 0.001).
References
Ref 1 SIRT1-autophagy axis inhibits excess iron-induced ferroptosis of foam cells and subsequently increases IL-1 and IL-18. Biochem Biophys Res Commun. 2021 Jul 5;561:33-39. doi: 10.1016/j.bbrc.2021.05.011. Epub 2021 May 15.
Ref 2 [MicroRNA-132 promotes atherosclerosis by inducing mitochondrial oxidative stressmediated ferroptosis]. Nan Fang Yi Ke Da Xue Xue Bao. 2022 Jan 20;42(1):143-149. doi: 10.12122/j.issn.1673-4254.2022.01.18.
Ref 3 PDSS2 Inhibits the Ferroptosis of Vascular Endothelial Cells in Atherosclerosis by Activating Nrf2. J Cardiovasc Pharmacol. 2021 Apr 29;77(6):767-776. doi: 10.1097/FJC.0000000000001030.