Shiyu Zhang, Shijie Li, Lin Cui, Shiyang Xie, Youping Wang

Division of Cardiology and Central Laboratory, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, People’s Republic of China

Correspondence: Youping Wang, Division of Cardiology and Central Laboratory, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, 19 Renmin Road, Zhengzhou, 450000, People’s Republic of China, Tel +86-371-66248345, Email wangyp8@163.com

Background: Angiotensin II (Ang II)-triggered endothelial inflammation is a critical mechanism contributing to Ang II-related cardiovascular diseases. The inflammation is highly correlated with mitochondrial function. Although astragaloside IV (AS-IV), a primary bioactive ingredient extracted from the traditional Chinese medicine Astragalus membranaceus Bunge that can effectively treat numerous cardiovascular diseases, posses the actions of antiinflammation and antioxidation in vivo, limited data are made available on the impacts of AS-IV on mitochondrial function in endothelial inflammation triggered by Ang II. This study was performed to evaluate the in vitro actions of AS-IV on Ang II-triggered inflammatory responses in endothelial cells, and to further clarify the potential role of mitochondria in the actions.
Methods: Human umbilical vein endothelial cells (HUVECs) were preincubated with AS-IV and then exposed to Ang II for 12 h.
Results: The exposure of HUVECs to Ang II triggered cytokine and chemokine production, the upregulation of adhesive molecules, monocyte attachment, and nuclear factor-kappa B activation. Additionally, our results showed that the inflammatory responses triggered by Ang II were associated with the impairment of mitochondrial function, as evidenced by the reductions of mitochondrial membrane potential, ATP synthesis, and mitochondrial complexes I and III activities. Moreover, the concentrations of malondialdehyde, cellular reactive oxygen species, and mitochondrial superoxide enhanced after HUVECs challenged with Ang II, which were concurrent with the decreases in total superoxide dismutase (SOD) and its isoenzyme activities such as Mn-SOD. These Ang II–induced alterations were reversed by preincubation with AS-IV.
Conclusion: Our data indicate that AS-IV attenuates Ang II-triggered endothelial inflammation possibly via ameliorating mitochondrial function.

Keywords: astragaloside IV, angiotensin II, mitochondria, inflammation, endothelial cells