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

Lianyue Ma,Cheng Zhang,Xiaoling Liu,Mei Ni,Yun Zhang,Xingli Xu,Panpan Hao,Yuxia Zhao,Shanying Huang,Xiaoyan Yang,Huixia Lu

doi:10.18632/oncotarget.7477

Lianyue Ma, Cheng Zhang + Show 9 more

Open Access

PDF Available

https://doi.org/10.18632/oncotarget.7477

Copy DOI

Export

Save

Cite

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

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.

Highlights

Acute myocardial syndrome (ACS) triggered by atherosclerotic plaque hemorrhage or plaque rupture accounts for substantial morbidity and mortality worldwide [1, 2]
Vasa vasorum (VV) neovascularization contributes to atherogenesis and its expansion and distribution is correlated with intraplaque expression of angiogenic factors
Vasa vasorum (VV) neovascularization is closely associated with atherogenesis [3,4,5].The extent and distribution of VV neovascularization in atherosclerotic plaques is regulated by numerous angiogenic factors

Summary

Introduction

Acute myocardial syndrome (ACS) triggered by atherosclerotic plaque hemorrhage or plaque rupture accounts for substantial morbidity and mortality worldwide [1, 2]. Vasa vasorum (VV) neovascularization is closely associated with atherogenesis [3,4,5].The extent and distribution of VV neovascularization in atherosclerotic plaques is regulated by numerous angiogenic factors. The vascular endothelial growth factor (VEGF) family and angiopoietin/Tie system play prominent roles. Angiopoietin 1 (ANGPT-1), a member of the angiopoietin/Tie system, blocks VEGF-induced vascular permeability and stabilizes the interaction between endothelial cells and supporting cells, whereas, ANGPT-2, an ANGPT-1 antagonist, leads to vascular destabilization or regression [8,9,10]. Reduced ANGPT-1 and increased ANGPT-2 levels are observed in vulnerable plaques of human carotid artery [11]. In the atherosclerotic plaques with high microvessel density, the ratio of ANGPT-1 to ANGPT-2 is in favor of ANGPT-2 [12]

Methods

Results

Conclusion