QiShenYiQi pill inhibits atherosclerosis by promoting reverse cholesterol transport PPARγ-LXRα/β-ABCA1 pathway.

QiShenYiQi pill (QSYQ), a Chinese compound medicine, originate from BuYangHuanWu decoction in the Qing dynasty, and has been used to treat ischemic cardiovascular diseases for more than two hundred years in China. Multi-central randomized double-blind controlled studies have proved that QSYQ has similar efficacy as enteric coated aspirin in the secondary prevention of myocardial infarction. The aim of study was to explore the effect of QSYQ on reverse cholesterol transport (RCT) pathway during atherosclerosis. Eight-week-old male apoE−/− mice (on the gene background of C57BL/6J) were fed with a high-fat western diet and treated with low dose and high dose of QSYQ, as well as the positive control agent, liver X receptor-α (LXR-α) agonist GW3965. Eight weeks later, mice were sacrificed and the aorta was collected for atherosclerotic analysis. The aortic root was stained with Oil red O to evaluate the area of atherosclerotic lesion, and stained with immunohistochemistry to analyze the intra-plaque component and RCT protein in atherosclerotic plaque. The thoracic aorta was used to detect differentially expressed genes by comparative transcriptome RNA-seq and the protein expression of RCT pathway by western blotting. After eight weeks of treatment, we found that both of QSYQ and LXR-α agonist reduced atherosclerotic plaque area significantly, and decreased the intra-plaque component, including the lipid, the smooth muscle cell and the macrophage. Compared with the control group, there were 49 differentially expressed genes in low-dose QSYQ group, including 21 up-regulated genes and 28 down-regulated genes. The results of GO and KEGG analysis showed that the differentially expressed genes mainly concentrated in the negative regulation of lipid biosynthesis, positive regulation of lipid metabolism, cell response to lipids, negative regulation of lipid storage, fatty acid degradation, and glycerol ester metabolism. Both of QSYQ and LXR-α agonist reduced the protein expression of CD36 and increased the protein expression of PPARγ-LXRα/β-ABCA1 in atherosclerotic plaque. The anti-atherosclerotic mechanism of QSYQ was involved in inhibiting lipid phagocytosis and promoting reverse cholesterol transport, therefore reducing lipid deposition and inflammatory cells in plaque. [Display omitted] • QSYQ attenuated atherosclerotic lesions. • QSYQ reduced lipid deposition and inflammatory cells. • QSYQ promoted reverse cholesterol transport signaling pathway. [ABSTRACT FROM AUTHOR]