Hypoxia serves a key function in the upregulated expression of vascular adhesion protein‑1 in vitro and in a rat model of hemorrhagic shock.

Abstract

Hemorrhagic shock following major trauma results in mortality, but the function of vascular adhesion protein‑1 (VAP‑1), implicated in intracranial hemorrhage, remains unknown. This study aimed to determine whether expression of the AOC3 gene and its encoded protein, VAP‑1, is altered by hypoxia. Rat hepatic sinusoidal endothelial cells (RHSECs) and rat intestinal microvascular endothelial cells (RIMECs) were transduced with a viral vector carrying AOC3, and AOC3 mRNA expression levels were measured by reverse transcription‑quantitative polymerase chain reaction. VAP‑1 protein expression levels were measured by western blot analysis and compared between normoxic and hypoxic conditions. Following this, AOC3 mRNA and VAP‑1 protein expression levels in hepatic and intestinal tissues were assessed in a rat model of hemorrhagic shock with or without fluid resuscitation; and serum semicarbazide‑sensitive amine oxidase (SSAO) activity was measured by fluorometric assays. The effects of 2‑bromoethylamine (2‑BEA) on AOC3/VAP‑1 levels and 24 h survival were investigated. AOC3 mRNA and VAP‑1 protein levels were increased in RHSECs and RIMECs by hypoxia, and in hepatic and intestinal tissues from rats following hemorrhagic shock. Hypoxia increased serum SSAO activity in these animals. 2‑BEA reduced AOC3 mRNA and VAP‑1 protein levels in hepatic and intestinal tissues from rats following hemorrhagic shock, and appeared to improve survival in animals not receiving resuscitation following hemorrhagic shock. In conclusion, hemorrhagic shock upregulates AOC3/VAP‑1 expressions, and this potentially occurs via hypoxia. Therefore, inhibition of VAP‑1 may be beneficial in the setting of hemorrhagic shock. Further studies are required to confirm these findings and to establish whether VAP‑1 may be a valid target for the development of novel therapies for hemorrhagic shock.

• Authors: Yuxing Zhang, Wei Yi, Jun Yao, Xiaojun Yu, Cheng Qian, Zhiqian Hu
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 16 Issue 2 Pg. 1189-1199 (Aug 2017) ISSN: 1791-3004 [Electronic] Greece
• PMID: 28627649 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Cell Adhesion Molecules
• Ethylamines
• 2-bromoethylamine
• Carbon Dioxide
• Amine Oxidase (Copper-Containing)
• vascular adhesion protein-1, rat
• Oxygen

Topics

• Amine Oxidase (Copper-Containing) (antagonists & inhibitors, genetics, metabolism)
• Animals
• Biomarkers
• Carbon Dioxide (metabolism)
• Cell Adhesion Molecules (antagonists & inhibitors, genetics, metabolism)
• Disease Models, Animal
• Endothelial Cells (metabolism)
• Ethylamines (pharmacology)
• Gene Expression Regulation
• Intestinal Mucosa (metabolism)
• Male
• Oxygen (metabolism)
• Rats
• Resuscitation
• Shock, Hemorrhagic (drug therapy, genetics, metabolism, mortality)