Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00102)
Name
Cardiovascular diseases
ICD
ICD-11: BE2Z
Full List of Target(s) of This Ferroptosis-centered Disease
Transferrin receptor protein 1 (TFRC)
 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 Marker/Suppressor/Driver
Responsed Disease Cardiovascular diseases [ICD-11: BE2Z]
Responsed Drug Sesamin Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model rHTs (Rat hippocampal tissues)
In Vivo Model
Forty specific pathogen-free normal Sprague Dawley (SD) rats (7 weeks old and 251-275 g in weight) were supplied by Charles River Laboratories. The SD rats were randomly allocated into five groups (n = 8). In the PM2.5 exposure group, the rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. In the saline control group, the SD rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and intratracheally instilled with 0.9% saline (1 mL per kg b.w.) every other day for a total of three times. In the Ses pretreatment groups, the SD rats were gavaged with low (L-Ses, 40 mg per kg b.w), medium (M-Ses, 80 mg per kg b.w.), and high (H-Ses, 160 mg per kg b.w.) doses of Ses. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times.

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Response regulation Sesamin pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis.
Solute carrier family 40 member 1 (SLC40A1)
 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 Marker/Suppressor
Responsed Disease Cardiovascular diseases [ICD-11: BE2Z]
Responsed Drug Sesamin Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model rHTs (Rat hippocampal tissues)
In Vivo Model
Forty specific pathogen-free normal Sprague Dawley (SD) rats (7 weeks old and 251-275 g in weight) were supplied by Charles River Laboratories. The SD rats were randomly allocated into five groups (n = 8). In the PM2.5 exposure group, the rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. In the saline control group, the SD rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and intratracheally instilled with 0.9% saline (1 mL per kg b.w.) every other day for a total of three times. In the Ses pretreatment groups, the SD rats were gavaged with low (L-Ses, 40 mg per kg b.w), medium (M-Ses, 80 mg per kg b.w.), and high (H-Ses, 160 mg per kg b.w.) doses of Ses. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times.

    Click to Show/Hide
Response regulation Sesamin pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 4 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Cardiovascular diseases [ICD-11: BE2Z]
Responsed Drug Astragaloside IV Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model HUVECs (Human umbilical vein endothelial cells)
Response regulation Astragaloside IV partially upregulated the levels of SLC7A11 and GPX4 expression which were reduced by LPC. The LPC-suppressed proliferation and LPC-induced apoptosis and senescence of endothelial cells were greatly attenuated by AS-IV treatment. In conclusion, AS-IV could serve as a novel drug for treating ferroptosis-related cardiovascular diseases.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Suppressor
Responsed Disease Cardiovascular diseases [ICD-11: BE2Z]
Responsed Regulator hsa-miR-124-3p (miRNA) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model hAAFs (Human aortic adventitial fibroblasts)
Response regulation UII inhibited miR-124 expression through up-regulating circ0004372 expression, thereby promoting SERTAD4 expression. UII significantly promoted the generation of ROS, MDA and 4-HNE, reduced the activities of SOD, GST and GR, increased Fe2+ concentration and inhibited GPX4 expression through circ0004372/ miR-124/SERTAD4 for cardiovascular diseases.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Suppressor
Responsed Disease Cardiovascular diseases [ICD-11: BE2Z]
Responsed Regulator Circ0004372 (circRNA) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model hAAFs (Human aortic adventitial fibroblasts)
Response regulation UII inhibited miR-124 expression through up-regulating circ0004372 expression, thereby promoting SERTAD4 expression. UII significantly promoted the generation of ROS, MDA and 4-HNE, reduced the activities of SOD, GST and GR, increased Fe2+ concentration and inhibited GPX4 expression through circ0004372/miR-124/SERTAD4 for cardiovascular diseases.
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Suppressor
Responsed Disease Cardiovascular diseases [ICD-11: BE2Z]
Responsed Regulator SERTA domain-containing protein 4 (SERTAD4) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model hAAFs (Human aortic adventitial fibroblasts)
Response regulation UII inhibited miR-124 expression through up-regulating circ0004372 expression, thereby promoting SERTAD4 expression. UII significantly promoted the generation of ROS, MDA and 4-HNE, reduced the activities of SOD, GST and GR, increased Fe2+ concentration and inhibited GPX4 expression through circ0004372/miR-124/ SERTAD4 for cardiovascular diseases.
Ferritin heavy chain (FTH1)
 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 Marker/Suppressor
Responsed Disease Cardiovascular diseases [ICD-11: BE2Z]
Responsed Drug Sesamin Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model rHTs (Rat hippocampal tissues)
In Vivo Model
Forty specific pathogen-free normal Sprague Dawley (SD) rats (7 weeks old and 251-275 g in weight) were supplied by Charles River Laboratories. The SD rats were randomly allocated into five groups (n = 8). In the PM2.5 exposure group, the rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. In the saline control group, the SD rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and intratracheally instilled with 0.9% saline (1 mL per kg b.w.) every other day for a total of three times. In the Ses pretreatment groups, the SD rats were gavaged with low (L-Ses, 40 mg per kg b.w), medium (M-Ses, 80 mg per kg b.w.), and high (H-Ses, 160 mg per kg b.w.) doses of Ses. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times.

    Click to Show/Hide
Response regulation Sesamin pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis.
Cystine/glutamate transporter (SLC7A11)
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Cardiovascular diseases [ICD-11: BE2Z]
Responsed Drug Astragaloside IV Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model HUVECs (Human umbilical vein endothelial cells)
Response regulation Astragaloside IV partially upregulated the levels of SLC7A11 and GPX4 expression which were reduced by LPC. The LPC-suppressed proliferation and LPC-induced apoptosis and senescence of endothelial cells were greatly attenuated by AS-IV treatment. In conclusion, AS-IV could serve as a novel drug for treating ferroptosis-related cardiovascular diseases.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Cardiovascular diseases [ICD-11: BE2Z]
Responsed Drug Sesamin Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model rHTs (Rat hippocampal tissues)
In Vivo Model
Forty specific pathogen-free normal Sprague Dawley (SD) rats (7 weeks old and 251-275 g in weight) were supplied by Charles River Laboratories. The SD rats were randomly allocated into five groups (n = 8). In the PM2.5 exposure group, the rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. In the saline control group, the SD rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and intratracheally instilled with 0.9% saline (1 mL per kg b.w.) every other day for a total of three times. In the Ses pretreatment groups, the SD rats were gavaged with low (L-Ses, 40 mg per kg b.w), medium (M-Ses, 80 mg per kg b.w.), and high (H-Ses, 160 mg per kg b.w.) doses of Ses. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times.

    Click to Show/Hide
Response regulation Sesamin pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis.
References
Ref 1 Sesamin attenuates PM(2.5)-induced cardiovascular injury by inhibiting ferroptosis in rats. Food Funct. 2021 Dec 13;12(24):12671-12682. doi: 10.1039/d1fo02913d.
Ref 2 Astragaloside IV Inhibits Bleomycin-Induced Ferroptosis in Human Umbilical Vein Endothelial Cells by Mediating LPC. Oxid Med Cell Longev. 2021 Nov 1;2021:6241242. doi: 10.1155/2021/6241242. eCollection 2021.
Ref 3 Urotensin II activates the ferroptosis pathway through circ0004372/miR-124/SERTAD4 to promote the activation of vascular adventitial fibroblasts. Gen Physiol Biophys. 2022 Sep;41(5):381-392. doi: 10.4149/gpb_2022027.