Shexiang Baoxin Pill Attenuates Ischemic Injury by Promoting Angiogenesis by Activation of Aldehyde Dehydrogenase 2.

Abstract

ABSTRACT:

Promoting angiogenesis is a critical treatment strategy for ischemic cardiovascular diseases. Shexiang Baoxin Pill (SBP), a traditional Chinese medicine, has been reported to be capable of relieving angina and improve heart function by promoting angiogenesis. The aim of this study was to determine the role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in SBP-induced angiogenesis. Left femoral artery ligation was performed in wild-type mice (WT) and ALDH2 knockout mice, which were administrated with SBP (20 mg/kg/d) or equal volume saline per day by gastric gavage for 2 weeks. Perfusion recovery, angiogenesis in chronic hind limb ischemia, was significantly improved in the WT + SBP group than in the WT group. However, these beneficial effects were absent in ALDH2 knockout mice. In vitro, hypoxia impaired the ability of proliferation, migration and tube formation, sprouting angiogenesis, and promoted apoptosis in cardiovascular microvascular endothelial cells, whereas the hypoxia damage was restored by SBP. The protective effect of SBP was remarkably weakened by ALDH2 knockdown. Furthermore, SBP suppressed hypoxia-induced ALDH2/protein kinase B (AKT)/mammalian target of rapamycin pathways. In conclusion, this study demonstrated that SBP protected lower limb from ischemia injury through the ALDH2-dependent pathway. The protective mechanism of SBP in cardiovascular microvascular endothelial cells was partly mediated through ALDH2/AKT/mammalian target of rapamycin pathways.

• Authors: Jingjing Hu, Yongchao Zhao, Yonghui Wu, Kun Yang, Kai Hu, Aijun Sun, Junbo Ge
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 77 Issue 3 Pg. 408-417 (03 01 2021) ISSN: 1533-4023 [Electronic] United States
• PMID: 33662981 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Angiogenesis Inducing Agents
• Drugs, Chinese Herbal
• shexiang baoxin
• ALDH2 protein, mouse
• Aldehyde Dehydrogenase, Mitochondrial
• Aldh2 protein, rat
• Proto-Oncogene Proteins c-akt

Topics

• Aldehyde Dehydrogenase, Mitochondrial (genetics, metabolism)
• Angiogenesis Inducing Agents (pharmacology)
• Animals
• Cell Hypoxia
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology)
• Endothelial Cells (drug effects, enzymology)
• Enzyme Activation
• Hindlimb (blood supply)
• Ischemia (drug therapy, enzymology, physiopathology)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Neovascularization, Physiologic (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats, Sprague-Dawley
• Regional Blood Flow
• Signal Transduction
• Mice
• Rats