J Korean Med Sci.  2013 May;28(5):725-730. 10.3346/jkms.2013.28.5.725.

COMP-Angiopoietin-1 Promotes Cavernous Angiogenesis in a Type 2 Diabetic Rat Model

• Kim SO
• Lee HS
• Ahn K
• Park K

• KMID: 1777560
• DOI: http://doi.org/10.3346/jkms.2013.28.5.725

Abstract

Cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) is an angiogenic factor for vascular angiogenesis. The aim was to investigate the effect of an intracavernosal injection of COMP-Ang1 on cavernosal angiogenesis in a diabetic rat model. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats made up the experimental group (1 yr old) and Long-Evans Tokushima Otsuka (LETO) rats made up the control group. The experimental group was divided into vehicle only, 10 microg COMP-Ang1, and 20 microg COMP-Ang1. COMP-Ang1 was injected into the corpus cavernosum of the penis. After 4 weeks, the penile tissues of the rats were obtained for immunohistochemistry and Western blot analysis. The immunoreactivity of PECAM-1 and VEGF was increased in the COMP-Ang1 group compared with the vehicle only group. Moreover, the expression of PECAM-1 and VEGF was notably augmented in the 20 microg Comp Ang-1 group. In the immunoblotting study, the expression of PECAM-1 and VEGF protein was significantly less in the OLEFT rats than in the control LETO rats. However, this expression was restored to control level after intracavernosal injection of COMP-Ang1. These results show that an intracavernosal injection of COMP-Ang1 enhances cavernous angiogenesis by structurally reinforcing the cavernosal endothelium.

Keyword

Erectile Dysfunction; Rats, Inbred OLETF; Angiogenesis; Angiopoietin-1

MeSH Terms

Angiopoietin-1/genetics/*metabolism
Animals
Antigens, CD31/metabolism
Blood Glucose/analysis
Blotting, Western
Body Weight
Cartilage Oligomeric Matrix Protein/genetics/*metabolism
Diabetes Mellitus, Experimental/*pathology
Immunohistochemistry
Male
Neovascularization, Physiologic/*drug effects
Penis/metabolism/pathology
Rats
Rats, Long-Evans
Recombinant Fusion Proteins/biosynthesis/genetics/*pharmacology
Vascular Endothelial Growth Factor A/metabolism
Angiopoietin-1
Antigens, CD31
Blood Glucose
Cartilage Oligomeric Matrix Protein
Recombinant Fusion Proteins
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1 Immunohistochemistry of PECAM-1 in penis tissue from the LETO (A), OLETF (B), OLETF+10 µg COMP-Ang1 (C), and OLETF+20 µg COMP-Ang1 (D) groups. Immunolabeling of PECAM-1 appears in brown. PECAM-1 is mainly expressed in the corpus cavernosal endothelium. Immunoblotting of PECAM-1 in the corpus cavernosum in the rat penis (E). The anti-PECAM antibodies recognized 130-kDa bands. Anti-actin antibody recognized the 42-kDa band. PECAM-1 protein expression decreased significantly in the OLETF group compared with the control LETO group. However, this expression increased significantly after intracavernosal injection of COMP-Ang1 (20 µg). The lower panel denotes the means and standard errors of 8 experiments for each condition as determined by densitometry relative to β-actin. *P < 0.05 vs LETO; †P < 0.05 vs OLETF. COMP-Ang1, COMP-Angiopoietin-1; LETO, Long-Evans Tokushima Otsuka rats; OLETF, Otsuka Long-Evans Tokushima fatty rats; PECAM-1, platelet-endothelial cell adhesion molecule-1.

• 

  Fig. 2 Immunohistochemical study of the expression of VEGF in penis tissue from the LETO (A), OLETF (B), OLETF+10 µg COMP-Ang1 (C), and OLETF+20 µg COMP-Ang1 (D) groups. Immunolabeling of VEGF appears in brown. VEGF is mainly expressed in the corpus cavernosal endothelium. Immunoblotting of VEGF in the corpus cavernosum in the rat penis (E). The anti-VEGF antibodies recognized 25-kDa bands. Anti-actin antibody recognized the 42-kDa band. VEGF protein expression decreased significantly in the OLETF group compared with the control LETO group. However, this expression was restored to the level of the control after intracavernosal injection of COMP-Ang1 in a dose-dependent manner. The lower panels denote the means and standard errors of 8 experiments for each condition as determined by densitometry relative to β-actin. *P < 0.05 vs LETO; †P < 0.05 vs OLETF. COMP-Ang1, COMP-Angiopoietin-1; LETO, Long-Evans Tokushima Otsuka rats; OLETF, Otsuka Long-Evans Tokushima fatty rats; VEGF, vascular endothelial growth factor.

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