Tongxinluo mitigates atherogenesis by regulating angiogenic factors and inhibiting vasa vasorum neovascularization in apolipoprotein E-deficient mice

// Lianyue Ma 1, 2 , Mei Ni 1 , Panpan Hao 1 , Huixia Lu 1 , Xiaoyan Yang 1 , Xingli Xu 1 , Cheng Zhang 1 , Shanying Huang 1 , Yuxia Zhao 1 , Xiaoling Liu 1, 2 , Yun Zhang 1, 2 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China 2 The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Shandong 250012, P.R. China Correspondence to: Xiaoling Liu, e-mail: xiaolingliusdu@163.com Yun Zhang, e-mail: zhangyun@sdu.edu.cn Keywords: atherogenesis, vasa vasorum, neovascularization, Tongxinluo Received: November 12, 2015      Accepted: February 08, 2016      Published: February 18, 2016 ABSTRACT Vasa vasorum (VV) neovascularization contributes to atherogenesis and its expansion and distribution is correlated with intraplaque expression of angiogenic factors. The present study investigated the roles of Tongxinluo (TXL), a traditional Chinese medication, on VV proliferation and atherogenesis. In vitro , TXL pre-treatment reversed the tumor necrosis factor-a (TNF-a) induced expression of vascular endothelial growth factor A (VEGF-A) and angiopoietin-1 (ANGPT-1) but not ANGPT-2, leading to increased ratio of ANGPT-1 to ANGPT-2. Consistently, TXL treatment (at a dosage of 0.38, 0.75, 1.5 g/kg/d, respectively) decreased the expression of VEGF-A while increased that of ANGPT-1 in early atherosclerotic lesions of apolipoprotein E deficient (apoE-/-) mice. On aortic ring assay, microvessels sprouting from aortas were significantly inhibited in TXL-treated mice. Moreover, VV neovascularization in plaques was markedly reduced with TXL treatment. Histological and morphological analysis demonstrated that TXL treatment reduced plaque burden, plaque size and changed the plaque composition. These data suggest that TXL inhibits early atherogenesis through regulating angiogenic factor expression and inhibiting VV proliferation in atherosclerotic plaque. Our study shed new light on the anti-atherosclerotic effect of TXL.