Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00099)
Name
Chronic heart failure
ICD
ICD-11: BD1Z
Full List of Target(s) of This Ferroptosis-centered Disease
Unspecific Target
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Responsed Disease Chronic heart failure [ICD-11: BD1Z]
Responsed Regulator Mitogen-activated protein kinase kinase kinase 11 (MAP3K11) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Necroptosis hsa04217
NF-kappa B signaling pathway hsa04064
Cell Process Cell ferroptosis
Cell pyroptosis
In Vitro Model rHTs (Rat hippocampal tissues)
In Vivo Model
Male wild-type (WT) C57BL/6J mice aged 8 weeks were obtained from the Experimental Animal Center, Guangzhou University of Chinese Medicine. Sham and TAC mice received corresponding isotype i.p. injections. TAC + AAVMLK3- mice were generated by intravenous (i.v.) injection of adeno-associated viral vector-MLK3 vector (AAVMLK3-) (GenePharma, Shanghai, China) 14 and 21 days before TAC surgery. Sham + AAVNC and TAC + AAVNC mice received AAVNC i.v. injections. TAC + antagomir and TAC + agomir were generated by i.v. injection of antagomir and agomir (30 pmol/g) 14 and 21 days before TAC surgery, respectively.

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Response regulation MLK3 (MAP3K11) mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of chronic heart failure (CHF). Promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Responsed Disease Chronic heart failure [ICD-11: BD1Z]
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Necroptosis hsa04217
NF-kappa B signaling pathway hsa04064
Cell Process Cell ferroptosis
Cell pyroptosis
In Vitro Model rHTs (Rat hippocampal tissues)
In Vivo Model
Male wild-type (WT) C57BL/6J mice aged 8 weeks were obtained from the Experimental Animal Center, Guangzhou University of Chinese Medicine. Sham and TAC mice received corresponding isotype i.p. injections. TAC + AAVMLK3- mice were generated by intravenous (i.v.) injection of adeno-associated viral vector-MLK3 vector (AAVMLK3-) (GenePharma, Shanghai, China) 14 and 21 days before TAC surgery. Sham + AAVNC and TAC + AAVNC mice received AAVNC i.v. injections. TAC + antagomir and TAC + agomir were generated by i.v. injection of antagomir and agomir (30 pmol/g) 14 and 21 days before TAC surgery, respectively.

    Click to Show/Hide
Response regulation MLK3 (MAP3K11) mainly regulates the JNK/ p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of chronic heart failure (CHF). Promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Responsed Disease Chronic heart failure [ICD-11: BD1Z]
Responsed Regulator mmu-miR-351-3p (miRNA) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Necroptosis hsa04217
NF-kappa B signaling pathway hsa04064
Cell Process Cell ferroptosis
Cell pyroptosis
In Vitro Model rHTs (Rat hippocampal tissues)
In Vivo Model
Male wild-type (WT) C57BL/6J mice aged 8 weeks were obtained from the Experimental Animal Center, Guangzhou University of Chinese Medicine. Sham and TAC mice received corresponding isotype i.p. injections. TAC + AAVMLK3- mice were generated by intravenous (i.v.) injection of adeno-associated viral vector-MLK3 vector (AAVMLK3-) (GenePharma, Shanghai, China) 14 and 21 days before TAC surgery. Sham + AAVNC and TAC + AAVNC mice received AAVNC i.v. injections. TAC + antagomir and TAC + agomir were generated by i.v. injection of antagomir and agomir (30 pmol/g) 14 and 21 days before TAC surgery, respectively.

    Click to Show/Hide
Response regulation MLK3 (MAP3K11) mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of chronic heart failure (CHF). Promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC.
References
Ref 1 Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload. Cell Death Dis. 2020 Jul 24;11(7):574. doi: 10.1038/s41419-020-02777-3.