Astragaloside IV Attenuated 3,4-Benzopyrene-Induced Abdominal Aortic Aneurysm by Ameliorating Macrophage-Mediated Inflammation.

Shaoze Wu,Yigen Shen,Luyuan Tao,Yingying Zhou,Jiaoni Wang,Kaiyu Huang,Kangting Ji,Jinsheng Wang,Saroj Thapa,Jie Wang,Yangjing Xue

doi:10.3389/fphar.2018.00496

Abstract

Abdominal aortic aneurysm (AAA), characterized by macrophage infiltration-mediated inflammation and oxidative stress, is a potentially fatal disease. Astragaloside IV (AS-IV) has been acknowledged to exhibit antioxidant and anti-inflammatory properties. This study was designed to investigate the protective effect of AS-IV against AAA formation induced by 3,4-benzopyrene (Bap) and angiotensin II (Ang II), and to explore probable mechanisms. Results showed that AS-IV decreased AAA formation, and reduced macrophage infiltration and expression of matrix metalloproteinase. Furthermore, AS-IV abrogated Bap-/Ang II-induced NF-κB activation and oxidative stress. In vitro, AS-IV inhibition of macrophage activation and NF-κB was correlated with increased phosphorylation of phosphatidylinositol 3-kinase (PI3-K)/AKT. Together, our findings suggest that AS-IV has potential as an intervention in the formation of AAA.Highlights(1)The protective effect of Astragaloside IV (AS-IV) on abdominal aortic aneurysm (AAA) is associated with its suppressing effects on inflammation in the aortic wall.(2)AS-IV abrogated 3,4-benzopyrene (Bap)/angiotensin II (Ang II)-induced nuclear factor-κB (NF-κB) activation and oxidative stress.(3)AS-IV inhibited Bap-induced RAW264.7 macrophage cells activation by inhibiting oxidative stress and NF-κB activation through phosphatidylinositol 3-kinase (PI3-K)/AKT pathway.AS-IV is a potential preventive agent for cigarette smoking-related AAA.

Highlights

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, predominantly associated with risk factors that include age, male gender, and smoking
Macroscopic observation revealed that the aortic diameter was increased significantly in the Bap/angiotensin II (Ang II) group, which was significantly reduced in mice treated with high doses of Astragaloside IV (AS-IV)
The incidence of AAA was 83.3, 75, and 33.3% in the Bap-/Ang II-treated mice receiving no AS-IV, low-dose AS-IV, and high-dose AS-IV, respectively, while AAA was not observed in the control group (Figure 1B)

Summary

Introduction

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, predominantly associated with risk factors that include age, male gender, and smoking. It results in mortality in about 90% of cases (Golledge et al, 2006; Hellenthal et al, 2009a,b). Macrophages secrete monocyte chemoattractant protein-1 to recruit monocytes and additional macrophages to the vessel wall, and produce proinflammatory cytokines and proteases that maintain chronic vascular inflammation and extracellular matrix destruction, leading to AAA formation (Daugherty and Cassis, 2004; Shimizu et al, 2006; Lai C.H. et al, 2013; Wang et al, 2013). Inflammatory responses can promote the development of aneurysms by enhancing the production of ROS (Miller et al, 2002); reducing ROS production and inflammation may attenuate AAA (Cao et al, 2010; Wu et al, 2011)

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