Name	Diseases of the circulatory system
ICD	ICD-11: BE2Z

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and ICAM-1, downregulated those of KLF2 and Constitutive NOS (eNOS), and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.
Responsed Disease	Vascular diseases [ICD-11: BE2Z]
Responsed Drug	Atorvastatin		Approved	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	YTHDF2 regulates the stability of MAP2K4 and HPK/GCK-like kinase HGK (MAP4K4) mRNAs.This study identified that dasatinib and quercetin alleviate LPS-induced senescence in HUVECs via the TRAF6-MAPK-NF-Kappa-B axis in a YTHDF2-dependent manner, providing novel ideas for clinical treatment of age-related cardiovascular diseases.
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and Intercellular adhesion molecule 1 (ICAM1), downregulated those of KLF2 and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.
Responsed Disease	Vascular diseases [ICD-11: BE2Z]
Responsed Drug	Atorvastatin		Approved	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of VCAM-1 and ICAM-1, downregulated those of Krueppel-like factor 2 (KLF2) and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.
Responsed Disease	Vascular diseases [ICD-11: BE2Z]
Responsed Drug	Atorvastatin		Approved	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	YTHDF2 regulates the stability of MAP kinase kinase 4 (MAP2K4) and MAP4K4 mRNAs.This study identified that dasatinib and quercetin alleviate LPS-induced senescence in HUVECs via the TRAF6-MAPK-NF-Kappa-B axis in a YTHDF2-dependent manner, providing novel ideas for clinical treatment of age-related cardiovascular diseases.
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	ALKBH5 is a negative regulator of post-ischemic angiogenesis via post-transcriptional modulation and destabilization of Protein Wnt-5a (WNT5A) mRNA in an m6A-dependent manner.
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	CMECs (Cardiac Microvascular Endothelial Cells )

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	The study aimed to find the role of m6A RNA demethylase alkB homolog 5 (ALKBH5) in ECs angiogenesis during ischemic injury. ALKBH5 helps in the maintenance of angiogenesis in endothelial cells following acute ischemic stress via reduced SPHK1 m6A methylation and downstream eNOS-AKT signaling.
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Vascular smooth muscle contraction			hsa04270
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HMVE (human microvascular endothelial cells (HMVE) were obtained from ATCC (ATCC-CRL1730))

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	ROS promotes ALKBH5 SUMOylation through activating ERK/EPHB2/JNK signaling, leading to inhibition of ALKBH5 m6A demethylase activity by blocking substrate accessibility. Post-translational modification of ALKBH5 regulates ROS-induced DNA damage response. ROS specifically promotes ALKBH5 but not FTO, METTL3 and METTL14 SUMOylation by enhancing the interaction of ALKBH5 and UBC9 and inhibiting the association between ALKBH5 and SUMO specific peptidase 1 (SENP1).
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Apoptosis			hsa04210
	Chemical carcinogenesis - reactive oxygen species			hsa05208
Cell Process	Oxygen species(ROS)-induced stress
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	For the ROS-induced DNA damage analysis, the indicated cell lines were treated with or without 100 uM hydrogen peroxide (H2O2), or 80 uM Carbonyl cyanide m-chlorophenylhydrazone (CCCP) for 6 hours. For the in vivo ROS study, DMSO and 5 mg/kg CCCP was intraperitoneally injected in to three pairs of mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	ROS promotes ALKBH5 SUMOylation through activating ERK/EPHB2/JNK signaling, leading to inhibition of ALKBH5 m6A demethylase activity by blocking substrate accessibility. Post-translational modification of ALKBH5 regulates ROS-induced DNA damage response. ROS specifically promotes ALKBH5 but not FTO, METTL3 and METTL14 SUMOylation by enhancing the interaction of ALKBH5 and Ubiquitin conjugating enzyme E2 I (UBE2I/UBC9) and inhibiting the association between ALKBH5 and SENP1.
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
	Chemical carcinogenesis - reactive oxygen species			hsa05208
Cell Process	Oxygen species(ROS)-induced stress
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	For the ROS-induced DNA damage analysis, the indicated cell lines were treated with or without 100 uM hydrogen peroxide (H2O2), or 80 uM Carbonyl cyanide m-chlorophenylhydrazone (CCCP) for 6 hours. For the in vivo ROS study, DMSO and 5 mg/kg CCCP was intraperitoneally injected in to three pairs of mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	FTO overexpression significantly upregulated the mRNA and protein levels of Vascular cell adhesion protein 1 (VCAM1) and ICAM-1, downregulated those of KLF2 and eNOS, and strongly attenuated the atorvastatin-mediated induction of KLF2 and eNOS expression. FTO could serve as a novel molecular target to modulate endothelial function in vascular diseases.
Responsed Disease	Vascular diseases [ICD-11: BE2Z]
Responsed Drug	Atorvastatin		Approved	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEK293T	Normal	Homo sapiens	CVCL_0063

Ref 1	N6-Methyladenosine Demethylase FTO (Fat Mass and Obesity-Associated Protein) as a Novel Mediator of Statin Effects in Human Endothelial Cells. Arterioscler Thromb Vasc Biol. 2022 May;42(5):644-658. doi: 10.1161/ATVBAHA.121.317295. Epub 2022 Mar 17.
Ref 2	Senolytics Cocktail Dasatinib and Quercetin Alleviate Human Umbilical Vein Endothelial Cell Senescence via the TRAF6-MAPK-NF-KappaB Axis in a YTHDF2-Dependent Manner. Gerontology. 2022;68(8):920-934. doi: 10.1159/000522656. Epub 2022 Apr 25.
Ref 3	Loss of m6A demethylase ALKBH5 promotes post-ischemic angiogenesis via post-transcriptional stabilization of WNT5A. Clin Transl Med. 2021 May;11(5):e402. doi: 10.1002/ctm2.402.
Ref 4	ALKBH5 Regulates SPHK1-Dependent Endothelial Cell Angiogenesis Following Ischemic Stress. Front Cardiovasc Med. 2022 Jan 20;8:817304. doi: 10.3389/fcvm.2021.817304. eCollection 2021.
Ref 5	Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response. Nucleic Acids Res. 2021 Jun 4;49(10):5779-5797. doi: 10.1093/nar/gkab415.