| Intracavernous delivery of synthetic angiopoietin-1 protein as a novel therapeutic strategy for erectile dysfunction in the type II diabetic db/db mouse. | |
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MedLine Citation:
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PMID: 20584113 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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INTRODUCTION: Patients with erectile dysfunction (ED) associated with type II diabetes often have impaired endothelial function and tend to respond poorly to oral phosphodiesterase type 5 inhibitors. Therefore, neovascularization is a promising strategy for curing diabetic ED. AIM: To determine the effectiveness of a soluble, stable, and potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous angiogenesis and erectile function in a mouse model of type II diabetic ED. Methods. Sixteen-week-old male db/db mice (in which obesity and type II diabetes are caused by a mutation in the leptin receptor) and control C57BL/6J mice were used and divided into four groups (N=14 per group): age-matched controls; db/db mice receiving two successive intracavernous injections of phosphate-buffered saline (PBS) (days -3 and 0; 20 µL); db/db mice receiving a single intracavernous injection of COMP-Ang1 protein (day 0; 5.8 µg/20 µL); and db/db mice receiving two successive intracavernous injections of COMP-Ang1 protein (days -3 and 0; 5.8 µg/20 µL). MAIN OUTCOME MEASURES: Two weeks later, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and stained with antibodies to platelet/endothelial cell adhesion molecule-1 (PECAM-1) (endothelial cell marker), phosphohistone H3 (PH3, a nuclear protein indicative of cell proliferation), phospho-endothelial nitric oxide synthase (eNOS), and eNOS. Penis specimens from a separate group of animals were used for cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) quantification. RESULTS: Local delivery of COMP-Ang1 protein significantly increased eNOS phosphorylation and cGMP and cAMP expression compared with that in the group treated with PBS. Repeated intracavernous injections of COMP-Ang1 protein completely restored erectile function and cavernous endothelial content through enhanced cavernous neoangiogenesis as evaluated by PECAM-1 and PH3 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, whereas a single injection of COMP-Ang1 protein elicited partial improvement. CONCLUSION: Cavernous neovascularization using recombinant Ang1 protein is a novel therapeutic strategy for the treatment of ED resulting from type II diabetes. |
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Authors:
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Hai-Rong Jin; Woo Jean Kim; Jae Sook Song; Shuguang Piao; Munkhbayar Tumurbaatar; Sun Hwa Shin; Min Ji Choi; Buyankhuu Tuvshintur; Kang-Moon Song; Mi-Hye Kwon; Guo Nan Yin; Gou Young Koh; Ji-Kan Ryu; Jun-Kyu Suh |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The journal of sexual medicine Volume: 7 ISSN: 1743-6109 ISO Abbreviation: J Sex Med Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-02 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101230693 Medline TA: J Sex Med Country: United States |
Other Details:
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Languages: eng Pagination: 3635-46 Citation Subset: IM |
Copyright Information:
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© 2010 International Society for Sexual Medicine. |
Affiliation:
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National Research Laboratory of Regenerative Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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