Astragaloside IV exerts angiogenesis and cardioprotection after myocardial infarction via regulating PTEN/PI3K/Akt signaling pathway.

Abstract

AIMS AND METHODS:

Acute myocardial infarction (AMI) is a common cardiovascular disease with high mortality. Astragaloside IV (AS-IV) was reported to have cardioprotective effect after AMI. We hypothesize that the cardioprotective role of AS-IV is exerted by enhancing angiogenesis via regulating PTEN/PI3K/Akt signaling pathway. To valid our hypothesis, AMI rats and human umbilical vein endothelial cells (HUVECs) were employed in our study.

KEY FINDINGS:

After treatment, cardiac function, survival rate, infarct size, pathological changes and fibrosis, cell apoptosis, ultrastructural changes, angiogenesis and expression of PTEN/PI3K/Akt signaling pathway were evaluated, respectively. In vitro study we detected proliferation, tube formation and signaling pathway activation of HUVECs treated with AS-IV, lentivirus overexpressed PTEN was employed to elucidate the potential mechanism. The results indicated that AS-IV administration significantly improved cardiac function and survival rate, limited infarct size, ameliorated pathological changes and fibrosis deposition, inhibited apoptosis, relieved ultrastructure injury and enhanced angiogenesis, PTEN/PI3K/Akt signaling pathway was activated simultaneously compared to the model group. In vitro study suggested that AS-IV treatment promoted cell proliferation and tube formation, and induced PTEN/PI3K/Akt signaling pathway activation. Importantly, overexpression of PTEN by lentivirus abolished AS-IV-induced angiogenesis.

SIGNIFICANCE:

Our study indicated that AS-IV could promote angiogenesis and cardioprotection after myocardial infarction. The mechanisms involve activation of PTEN/PI3K/Akt signaling pathway.

• Authors: Songyi Cheng, Xiaoxiao Zhang, Qian Feng, Jiandong Chen, Le Shen, Peng Yu, Li Yang, Daohai Chen, Haowen Zhang, Weixin Sun, Xiaohu Chen
• Journal: Life sciences (Life Sci) Vol. 227 Pg. 82-93 (Jun 15 2019) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 31004658 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inducing Agents
• Cardiotonic Agents
• Saponins
• Triterpenes
• Vascular Endothelial Growth Factor A
• astragaloside A
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase

Topics

• Angiogenesis Inducing Agents
• Animals
• Apoptosis (drug effects)
• Cardiotonic Agents
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Human Umbilical Vein Endothelial Cells
• Humans
• Male
• Myocardial Infarction (drug therapy, metabolism)
• Neovascularization, Pathologic (metabolism)
• PTEN Phosphohydrolase (drug effects, metabolism)
• Phosphatidylinositol 3-Kinases (drug effects, metabolism)
• Proto-Oncogene Proteins c-akt (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Saponins (metabolism, pharmacology)
• Signal Transduction (drug effects)
• Triterpenes (metabolism, pharmacology)
• Vascular Endothelial Growth Factor A (metabolism)