Neovastat (AE-941) inhibits the airway inflammation via VEGF and HIF-2 alpha suppression.

Abstract

Vascular endothelial growth factor (VEGF) contributes to airway inflammation and angiogenesis in asthma. Hypoxia inducible factor (HIF), the most potent regulator of VEGF, is a heterodimer of a constitutively expressed beta subunit and an oxygen-regulated alpha subunit (HIF-alpha). Three HIF-alpha isoforms have been described, of which HIF-2 alpha are abundantly expressed in lung tissue. Neovastat is a naturally occurring inhibitor of angiogenesis derived from marine cartilage. We previously reported that Neovastat can inhibit the airway inflammation in asthma. In this study, we hypothesized that the anti-inflammatory effect of Neovastat is mediated with inhibition of VEGF and HIF-2 alpha. BALB/c mice were immunized subcutaneously and challenged with inhaled ovalbumin (OVA). Neovastat was administrated by gavage three times with 12-h interval, beginning at 30 min before OVA inhalation. VEGF concentration in bronchoalveolar lavage fluid was measured by ELISA. We evaluate the expression of VEGF and HIF-2 alpha in lung tissue by immunohistochemistry. Mice treated with Neovastat had significantly reduced inflammatory cell count in BAL fluid compared with untreated asthmatic mice. Furthermore, Mice treated with Neovastat showed significantly reduced VEGF and HIF-2 alpha expression on lung tissue. These results suggest that anti-inflammatory effects of Neovastat could be linked to inhibition of VEGF and HIF-2 alpha.

• Authors: Sook Young Lee, Su-Mi Chung
• Journal: Vascular pharmacology (Vascul Pharmacol) 2007 Nov-Dec Vol. 47 Issue 5-6 Pg. 313-8 ISSN: 1537-1891 [Print] United States
• PMID: 17931982 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Basic Helix-Loop-Helix Transcription Factors
• Tissue Extracts
• Vascular Endothelial Growth Factor A
• shark cartilage extract
• endothelial PAS domain-containing protein 1
• Ovalbumin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Asthma (metabolism, pathology)
• Basic Helix-Loop-Helix Transcription Factors (antagonists & inhibitors, metabolism)
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Immunohistochemistry
• Inflammation (metabolism, prevention & control)
• Lung (drug effects, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Ovalbumin (immunology)
• Tissue Extracts (pharmacology)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, metabolism)