J Rhinol.  2022 Jul;29(2):82-87. 10.18787/jr.2021.00400.

The Roles of Vascular Endothelial Growth Factor, Angiostatin, and Endostatin in Nasal Polyp Development

• Hong TU
• Park SK

• KMID: 2532009
• DOI: http://doi.org/10.18787/jr.2021.00400

Abstract

Background and Objectives
Microvascular remodeling and angiogenesis are elements of tissue remodeling characteristic of chronic inflammatory diseases, including nasal polyps (NPs). Angiogenesis reflects the balance between the actions of pro- and anti-angiogenic factors. Many pro-angiogenic factors are known, including vascular endothelial growth factor (VEGF). A number of anti-angiogenic factors (e.g., angiostatin and endostatin) also has been identified. Our objective was to assess the roles of VEGF, angiostatin, and endostatin in NP development.
Methods
The expression levels of VEGF, angiostatin, and endostatin were measured in NPs harvested during endoscopic endonasal surgery and compared with those in inferior turbinate mucosa (control) samples acquired from patients with hypertrophic rhinitis without allergy. Western blotting and immunohistochemical staining were used to analyze all samples.
Results
The levels of VEGF and angiostatin were significantly higher in the NP subjects than in the controls. Neither the VEGF/angiostatin ratio nor the endostatin level differed significantly between the two groups. However, the VEGF/endostatin ratio was significantly higher in the NP than in the control group. Both the NP and control tissues were diffusely immunoreactive for VEGF, angiostatin, and endostatin.
Conclusion
NP-associated hypoxia can elevate angiostatin level; moreover, an imbalance in the VEGF/endostatin ratio can contribute to NP formation.

Keyword

Nasal polyps; Angiostatins; Endostatins; Vascular endothelial growth factor

Figure

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  Fig. 1 Western blotting exploring differences in the expression levels of VEGF, angiostatin, and endostatin between IT mucosal samples (n=12) and NPs (n=13). Equal amounts of cell lysates were separated on sodium dodecyl sulfate-polyacrylamide gels and transferred to membranes, which were then probed with antibodies against VEGF, endostatin, and angiostatin. Proteins were visualized using an electrochemiluminescence detection system. VEGF, vascular endothelial growth factor; IT, inferior turbinate; NP, nasal polyp.

• 

  Fig. 2 VEGF immunoreactivities of NPs and the IT mucosae. The horseradish peroxidase-based 3,3′-diaminobenzidine method was used. VEGF immunoreactivity was evident principally in stromal cells, including endothelial cells, fibroblasts, and inflammatory cells in both IT samples (A and B) and NP tissues (C and D) (magnification, ×5 [A and C] and ×20 [B and D]). VEGF, vascular endothelial growth factor; NP, nasal polyp; IT, inferior turbinate.

• 

  Fig. 3 Angiostatin immunoreactivities of NPs and IT mucosal samples. The horseradish peroxidase-based 3,3′-diaminobenzidine method was used. Immunoreactivity was evident principally in the submucosal inflammatory cells of the stroma and endothelial cells of both the IT samples (A and B) and NPs (C and D) (magnification, ×2.5 [A and C] and ×10 [B and D]). NP, nasal polyp; IT, inferior turbinate.

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  Fig. 4 Endostatin immunoreactivities in NPs and IT mucosal samples. The horseradish peroxidase-based 3,3′-diaminobenzidine method was used. Endostatin was strongly expressed in endothelial cells of the stromal vessels of both the IT tissues (A and B) and NPs (C and D) (magnification, ×5 [A and C] and ×10 [B and D]). NP, nasal polyp; IT, inferior turbinate.

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