Suxiaojiuxin Pill enhances atherosclerotic plaque stability by modulating the MMPs/TIMPs balance in apoE-deficient mice


Zhang, Jinbao; Zhuang, Pengwei; Lu, Zhiqiang; Zhang, Mixia; Zhang, Teng; Zhang, Yanjun; Wang, Jinlei; Liu, Dan; Tong, Yongling


Suxiaojiuxin Pill (SX) is a famous Chinese formulated product, which has been used to treat coronary heart disease and angina pectoris in China. This study was carried out to investigate the effect and possible mechanism of SX on the stability of atherosclerotic plaque in ApoE-deficient mice. 6~8 weeks old apoE-/- mice were fed with high fat diet (HFD) for developing artherosclerosis. After oral administration of SX for 8 weeks, histopathology of aortic plaque was done by Sudan III and H&E staining, and muscle protein detected by western blotting. The mRNA and proteins associated with aortic plaque stability were detected by RT-PCR and Western blotting (WB) respectively. SX treatment could not only reduce serum TG level and plaque area but also increase fibrous cap thickness and collagen content compared with model group. WB results showed that SX could increase [alpha]-smooth muscle actin ([alpha]-SMA), tissue inhibitor of metalloproteinase 1(TIMP-1) and TIMP-2 protein expression whereas decrease matrix metalloproteinase 2 (MMP-2) and MMP-9 protein expression. Moreover, SX could up-regulate expression of [alpha]-SMA mRNA and down-regulate expression of vascular endothelial growth factor (VEGF) mRNA. These results showed that SX could enhance atherosclerotic plaque stability in ApoE-deficient mice. The mechanism may be associated with modulating the MMPs/TIMPs balance.