Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00092)
Name
Essential hypertension
ICD
ICD-11: BA00
Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
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 Hypertension [ICD-11: BA00]
Responsed Regulator Aldo-keto reductase family 1 member C2 (AKR1C2) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
In Vivo Model
Aortic smooth muscle cells were isolated from wild-type male 6-8-week and CSE-knockout mice. Mice were sacrificed by decapitation, followed by separating the aorta via removing the fatty tissue and vascular adventitia. Then, the mouse aorta was cut into pieces and allowed for digestion for 8 h in the DMEM containing collagenase type 1. The obtained VSMCs were centrifuged at 300 xg for 5 min, and the pellet was resuspended in the DMEM supplemented with 10% FBS, 2 mM l-glutamine, and 100 U/mL penicillin/streptomycin. The medium was replaced every 2 days.

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Response regulation Aortic GPX4 (a core regulator of ferroptosis) significantly downregulated association with VSMC novel phenotype elevation in SHR rats and hypertension patients. The ferroptosis inhibitor ferrostatin-1 (Fer-1) administration blocked HHP-induced VSMC inflammatory (CXCL2 expression) and endothelial function inhibitory ( AKR1C2 expression) phenotyping switch association with elevation in the GPX4 expression, reduction in the reactive oxygen species (ROS), and lipid peroxidation production.
Unspecific Target
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Hypertension [ICD-11: BA00]
Responsed Drug Eucommia ulmoides Oliver-Tribulus terrestrisL Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Response regulation The active ingredients of Eucommia ulmoides Oliver-Tribulus terrestrisL (EUO-TT) drug pair may act on proteins associated with the neuroactive ligand-receptor interaction pathway to regulate ferroptosis in vascular neurons cells, ultimately affecting the onset and progression of hypertension.
References
Ref 1 Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife. 2014 May 20;3:e02523. doi: 10.7554/eLife.02523.
Ref 2 Eucommia ulmoides Oliver-Tribulus terrestris L. Drug Pair Regulates Ferroptosis by Mediating the Neurovascular-Related Ligand-Receptor Interaction Pathway- A Potential Drug Pair for Treatment Hypertension and Prevention Ischemic Stroke. Front Neurol. 2022 Mar 8;13:833922. doi: 10.3389/fneur.2022.833922. eCollection 2022.