期刊
PHARMACEUTICAL BIOLOGY
卷 61, 期 1, 页码 404-415出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/13880209.2023.2225543
关键词
Type 2 diabetes mellitus with atherosclerosis; Ox-LDL; ApoE(-/-); mice; HUVEC
This study confirms that HSYA can improve symptoms in a mouse model of T2DM/AS and elucidates the underlying mechanisms. HSYA effectively reduces atherosclerotic plaque formation in the T2DM/AS mouse model and inhibits HUVEC ferroptosis, while upregulating GSH-Px, SLC7A11, and GPX4 expression and inhibiting ACSL4 expression. Furthermore, HSYA downregulates miR-429 expression, further regulating SLC7A11 expression.
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 & mu;g/mL ox-LDL were used to construct a high lipid and high glucose cell model treated with 25 & mu;M 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.
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