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

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.