PIAS3 deficiency exacerbates the development of atherosclerosis in female ApoE knock-out mice
10.20039/j.cnki.1007-3949.2025.08.003
- VernacularTitle:PIAS3缺失促进雌性ApoE基因敲除小鼠动脉粥样硬化发展
- Author:
Chaochao LI
1
;
Huizi HUANG
1
;
Jingyi ZHANG
1
;
Hao FEI
1
;
Liwei YANG
1
;
Rong WANG
1
Author Information
1. 西安交通大学医学部转化医学研究院心血管研究所;西安交通大学医学部基础医学院实验动物学系,陕西省西安市 710061
- Publication Type:Journal Article
- Keywords:
atherosclerosis;
protein inhibitor of activated STAT3;
estrogen receptor α;
vascular smooth muscle cell
- From:
Chinese Journal of Arteriosclerosis
2025;33(8):665-672
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate whether protein inhibitor of activated STAT3(PIAS3)deficiency exacerbates the occurrence and development of atherosclerosis(As)in female ApoE knockout mice.Methods PIAS3 gene knockout mice with ApoE-/-background(PIAS3-/-/ApoE-/-)and their littermate PIAS3+/+/ApoE-/-mice were bred and fed with a high-fat/high-cholesterol diet for 12 weeks to induce As.Body weight(every week)and plasma lipid levels including to-tal cholesterol,triglyceride,high density lipoprotein cholesterol and non-high density lipoprotein cholesterol(every 4 weeks)of the mice were measured.Oil red O staining,HE staining,immunohistochemistry staining and immunofluores-cence staining were performed on mouse aortic tree and frozen sections of aortic root to evaluate the area,cellular composi-tion and stability of As plaques.Moreover,the expression of estrogen receptor α(ERα)and its co-localization with vas-cular smooth muscle cells(VSMC)in plaques were determined by immunofluorescence staining.Results Compared with PIAS3+/+/ApoE-/-mice,PIAS3-/-/ApoE-/-mice showed no significant differences in body weight,major organ weight(heart,liver,spleen,kidney and epididymal fat)and plasma lipid levels;however,PIAS3 deficiency promoted the forma-tion of As in female PIAS3-/-/ApoE-/-mice.Compared with PIAS3+/+/ApoE-/-mice,PIAS3-/-/ApoE-/-mice showed an increased lipid accumulation and a decreased VSMC content in As plaques(P＜0.05),leading to a decrease in plaque stability.In addition,the expression of ERα in the As plaques of PIAS3-/-/ApoE-/-mice was significantly downregulated(P＜0.05),and there was a obvious co-localization between ERα and VSMC.The reduction of VSMC content in PIAS3-/-/ApoE-/-mouse plaques might lead to a decrease of ERα expression,thereby weakening the anti-As effect of es-trogen.Conclusion PIAS3 deficiency exacerbates the formation of As plaques in female PIAS3-/-/ApoE-/-mice,which might be due to the regulatory effect of PIAS3 on ERα expression in plaques.
