Novel treatment from a botanical formulation Si-Miao-Yong-an decoction inhibits vasa vasorum angiogenesis and stabilizes atherosclerosis plaques via the Wnt1/-catenin signalling pathway

Context: Si-Miao-Yong-An (SMYA) has been widely used for the clinical treatment of atherosclerosis (AS). Yet, its complete mechanism of action is not fully understood. Objective: To investigate the mechanism by which SMYA stabilizes AS plaques from the perspective of inhibiting vasa vasorum (VV) angiogenesis. Materials and methods: We used male ApoE(-/-) mice to establish an AS model. The mice were divided into model, SMYA (11.7 mg/kg/d), and simvastatin (SVTT) (2.6 mg/kg/d) groups. Mice were given SMYA or SVTT by daily gavage for 8 weeks. HE staining, immunofluorescence double-labelling staining, and immunohistochemical staining were used to observe the pathological changes in the plaques. Finally, the protein and mRNA expression levels of the Wnt1/b-catenin signalling pathway were detected by Western blot and qRT-PCR, respectively. Results: SMYA significantly attenuated cholesterol crystallization, and lipid accumulation in AS plaques, resulting in smaller plaque size (0.25mm(2) vs. 0.46mm(2)), and lowering ratio of plaque to lumen area (20.04% vs. 38.33%) and VV density (50.64/mm(2) vs. 98.02/mm(2)). Meanwhile, SMYA suppressed both the positive area percentage of Wnt1 (2.53 vs. 3.56), beta-catenin (3.33 vs. 5.65) and Cyclin D1 (2.10 vs. 3.27) proteins in the aortic root plaques, and mRNA expression of Wnt1 (1.38 vs. 2.09), b-catenin (2.05 vs. 3.25) and Cyclin D1 (1.39 vs. 2.57). Discussion and conclusions: SMYA has a protective effect against AS, which may be related to its anti-VV angiogenesis in plaques, suggesting that SMYA has the potential as a novel botanical formulation in the treatment of AS.