PMID- 37410531
OWN - NLM
STAT- MEDLINE
DCOM- 20230710
LR  - 20230718
IS  - 1744-5116 (Electronic)
IS  - 1388-0209 (Print)
IS  - 1388-0209 (Linking)
VI  - 61
IP  - 1
DP  - 2023 Dec
TI  - Hydroxysafflor yellow A inhibits endothelial cell ferroptosis in diabetic 
      atherosclerosis mice by regulating miR-429/SLC7A11.
PG  - 404-415
LID - 10.1080/13880209.2023.2225543 [doi]
AB  - CONTEXT: Ferroptosis may play an essential role in lipid peroxidation and 
      endothelial dysfunction of aortic endothelial cells (ECs) in type 2 diabetes 
      mellitus (T2DM) with atherosclerosis (AS). Hydroxysafflor yellow A (HSYA) has 
      shown substantial antioxidant stress and anti-ferroptosis. OBJECTIVE: This study 
      confirms whether HSYA improves symptoms in a mouse model of T2DM/AS and 
      elucidates the underlying mechanisms. MATERIALS AND METHODS: ApoE(-/-) mice were 
      fed with high fat combined with 30 mg/kg streptozotocin to establish a T2DM/AS 
      model. Then mice were treated with intraperitoneal injections of 2.25 mg/kg HSYA 
      for 12 weeks. Human Umbilical Vein Endothelial cells (HUVEC) induced by 33.3 mM 
      d-glucose +100 mug/mL ox-LDL were used to construct a high lipid and high glucose 
      cell model treated with 25 muM HSYA. The changes in oxidative stress- and 
      ferroptosis-related markers were detected, and the regulatory effect of HSYA on 
      the miR-429/SLC7A11 was also verified. Normal ApoE(-/-) mice or HUVEC cells were 
      used as the control group. RESULTS: HSYA effectively reduced atherosclerotic 
      plaque formation in the T2DM/AS mouse model and inhibited HUVEC ferroptosis, such 
      as upregulating GSH-Px, SLC7A11 and GPX4, but inhibited ACSL4. Furthermore, HSYA 
      also downregulated the expression of miR-429, which further regulated SLC7A11 
      expression. After miR-429 mimic or SLC7A11 siRNA transfection in the HUVEC, the 
      antioxidative stress and anti-ferroptosis effects of HSYA were significantly 
      abolished. CONCLUSIONS: HSYA is expected to become an important health drug to 
      prevent the occurrence and development of T2DM/AS.
FAU - Rong, Jianjie
AU  - Rong J
AD  - Department of Vascular Surgery, Suzhou TCM Hospital Affiliated to Nanjing 
      University of Chinese Medicine, Suzhou, P. R. China.
FAU - Li, Chuanyong
AU  - Li C
AD  - Department of Vascular Surgery, Suzhou TCM Hospital Affiliated to Nanjing 
      University of Chinese Medicine, Suzhou, P. R. China.
FAU - Zhang, Qiang
AU  - Zhang Q
AD  - Department of Vascular Surgery, Suzhou TCM Hospital Affiliated to Nanjing 
      University of Chinese Medicine, Suzhou, P. R. China.
FAU - Zheng, Guangfeng
AU  - Zheng G
AD  - Department of Vascular Surgery, Suzhou TCM Hospital Affiliated to Nanjing 
      University of Chinese Medicine, Suzhou, P. R. China.
FAU - Fan, Weijian
AU  - Fan W
AD  - Department of Vascular Surgery, Suzhou TCM Hospital Affiliated to Nanjing 
      University of Chinese Medicine, Suzhou, P. R. China.
FAU - Pan, Zhichang
AU  - Pan Z
AD  - Department of Vascular Surgery, Suzhou TCM Hospital Affiliated to Nanjing 
      University of Chinese Medicine, Suzhou, P. R. China.
FAU - Shi, Shuming
AU  - Shi S
AD  - Department of Vascular Surgery, Suzhou TCM Hospital Affiliated to Nanjing 
      University of Chinese Medicine, Suzhou, P. R. China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Pharm Biol
JT  - Pharmaceutical biology
JID - 9812552
RN  - 146087-19-6 (hydroxysafflor yellow A)
RN  - 0 (MicroRNAs)
RN  - 0 (Apolipoproteins E)
RN  - 0 (SLC7A11 protein, human)
RN  - 0 (Amino Acid Transport System y+)
RN  - 0 (MIRN429 microRNA, human)
RN  - 0 (MIRN429 microRNA, mouse)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Human Umbilical Vein Endothelial Cells
MH  - *Atherosclerosis/drug therapy/prevention & control/metabolism
MH  - Disease Models, Animal
MH  - *MicroRNAs/genetics/metabolism
MH  - Apolipoproteins E/metabolism/pharmacology
MH  - Amino Acid Transport System y+/metabolism
PMC - PMC10327525
OTO - NOTNLM
OT  - ApoE-/- mice
OT  - HUVEC
OT  - Ox-LDL
OT  - Type 2 diabetes mellitus with atherosclerosis
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2023/07/06 13:14
MHDA- 2023/07/10 06:42
PMCR- 2023/07/06
CRDT- 2023/07/06 11:53
PHST- 2023/07/10 06:42 [medline]
PHST- 2023/07/06 13:14 [pubmed]
PHST- 2023/07/06 11:53 [entrez]
PHST- 2023/07/06 00:00 [pmc-release]
AID - 2225543 [pii]
AID - 10.1080/13880209.2023.2225543 [doi]
PST - ppublish
SO  - Pharm Biol. 2023 Dec;61(1):404-415. doi: 10.1080/13880209.2023.2225543.