Therapeutic potential of astragalus polysaccharides in coronary heart disease: Insights into PCSK9/LDLR-mediated myocardial fibrosis

IF 2.5 4区综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES

Journal of Radiation Research and Applied Sciences Pub Date : 2025-08-19 DOI:10.1016/j.jrras.2025.101883

Wenwen Lin, Fanqi Kong, Mengmeng Zheng

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引用次数: 0

Abstract

Objective

This study aimed to explore whether Astragalus Polysaccharide (APS) regulates myocardial fibrosis in mice with coronary heart disease (CHD) via the PCSK9/LDLR pathway, and reveal its underlying mechanism.

Methods

Apolipoprotein E (ApoE) knockout mice were provided with a lipid-rich diet to induce coronary heart disease (CHD) and treated with low, medium, or high doses of Astragalus polysaccharides (APS). Heart mass, heart index, and serum lipids-including low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C)-were quantified using enzyme-linked immunosorbent assay (ELISA). Myocardial collagen volume fraction (CVF) was assessed by Masson's trichrome staining. Collagen I, collagen III, and α-smooth muscle actin (α-SMA) were examined using quantitative polymerase chain reaction (qPCR) and Western blot. Hepatic levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR) were quantified. Human umbilical vein endothelial cells (HUVECs) were used in vitro to examine APS effects on the PCSK9/LDLR pathway.

Results

In vivo, CHD model mice exhibited increased heart mass, heart index, myocardial interstitial collagen fibers, and CVF, accompanying the elevated expression of collagen I, collagen III, and α-SMA in myocardial tissue, and increased PCSK9 levels with decreased LDLR expression in liver tissue. APS treatment significantly (P < 0.05) improved these parameters, including a notable reduction in collagen deposition and lipid levels. In vitro, LPS treatment reduced the viability of HUVECs and resulted in elevated expression of collagen I, collagen III, α-SMA, and PCSK9, while LDLR levels were diminished. APS treatment alleviated the detrimental effects of LPS on HUVECs. Nonetheless, the beneficial effects of APS on LPS-treated HUVECs were abrogated by PCSK9 overexpression.

Conclusion

APS mitigates myocardial fibrosis in CHD mice through regulation of the PCSK9/LDLR pathway and enhancement of cardiac function.

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黄芪多糖对冠心病的治疗潜力：PCSK9/ ldlr介导的心肌纤维化

目的探讨黄芪多糖（Astragalus多糖，APS）是否通过PCSK9/LDLR通路调控冠心病小鼠心肌纤维化，并揭示其机制。方法采用高脂饮食诱导ApoE基因敲除小鼠，并分别给予低、中、高剂量黄芪多糖（黄芪多糖）治疗。采用酶联免疫吸附法（ELISA）定量测定心脏质量、心脏指数和血清脂质，包括低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、甘油三酯（TG）和高密度脂蛋白胆固醇（HDL-C）。心肌胶原体积分数（CVF）采用马氏三色染色法测定。采用定量聚合酶链反应（qPCR）和Western blot检测ⅰ型胶原、ⅲ型胶原和α-平滑肌肌动蛋白（α-SMA）。测定肝脏蛋白转化酶枯草素/克辛9型（PCSK9）和低密度脂蛋白受体（LDLR）水平。利用体外培养的人脐静脉内皮细胞（HUVECs）检测APS对PCSK9/LDLR通路的影响。结果在体内，冠心病模型小鼠心脏质量、心脏指数、心肌间质胶原纤维和CVF增加，心肌组织中I型胶原、III型胶原和α-SMA表达升高，肝组织中PCSK9水平升高，LDLR表达降低。APS处理显著改善了这些参数（P < 0.05），包括胶原沉积和脂质水平显著降低。在体外，LPS处理降低了huvec的活力，导致I型胶原、III型胶原、α-SMA和PCSK9的表达升高，而LDLR水平降低。APS处理减轻了LPS对HUVECs的有害影响。尽管如此，APS对lps处理的HUVECs的有益作用被PCSK9过表达所抵消。结论黄芪多糖通过调控PCSK9/LDLR通路，增强心功能，减轻冠心病小鼠心肌纤维化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Radiation Research and Applied Sciences MULTIDISCIPLINARY SCIENCES-

自引率

5.90%

发文量

130

审稿时长

16 weeks

期刊介绍： Journal of Radiation Research and Applied Sciences provides a high quality medium for the publication of substantial, original and scientific and technological papers on the development and applications of nuclear, radiation and isotopes in biology, medicine, drugs, biochemistry, microbiology, agriculture, entomology, food technology, chemistry, physics, solid states, engineering, environmental and applied sciences.