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J.-K. Suh, W.J. Kim, K.-M. Song, A. Limanjaya, K. Ghatak, N.N. Minh, S.-W. Park, J. Ock, J.-K. Ryu, PS-04-009 Vasohibin-1 is A Novel Therapeutic Target for Diabetic Erectile Dysfunction, The Journal of Sexual Medicine, Volume 14, Issue Supplement_4a, April 2017, Page e118, https://doi.org/10.1016/j.jsxm.2017.03.105
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Objective
Penile neovascularization is a promising strategy to treat intractable erectile dysfunction (ED). Vasohibin-1 (VASH1) is an angiogenesis-inhibiting factor synthesized by endothelial cells from the blood vessel. Here, we for the first time investigated the role of VASH1 in the corpus cavernosum and its effectiveness in penile erection by the local administration in the diabetic condition.
Methods
Diabetes was induced by intraperitoneal injection of streptozotocin into 8-week-old wild type C57BL/6 or VASH1 knockmale mice. At 8 weeks after the induction of diabetes, the animals were divided into 4 groups: controls, streptozotocin-induced diabetic mice receiving 2 successive intracavernous treatment of PBS, or VASH1 protein (1 μg and 4 μg in 20 μL of PBS, respectively). Two weeks after the treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histological and biochemical studies.
Results
The cavernous expression of VASH1 was down-regulated in both diabetic mice and patients with diabetic ED; VASH1 was mainly expressed in endothelial cells. VASH-1 knockout mice revealed decrease in cavernous endothelial and pericyte content compared with wild type mice, which resulted in deterioration of erectile function. Intracavernous delivery of VASH1 in diabetic mice induced significant restoration of erectile function, which reached up to 85% of control values at higher dose. VASH1 significantly increased cavernous endothelial cell and induced eNOS phosphorylation. VASH1 decreased extravasation of oxidized-LDL by restoring pericyte content and endothelial cell-cell junction proteins in the diabetic mice. By using proteome profiler array kit, we found that the induction of angiogenic factors, including angiopoietin-1, vascular endothelial growth factor, and basic fibroblasts growth factor, mainly in fibroblasts is a major molecular mechanism responsible for VASH1-mediated cavernous angiogenesis and subsequent restoration of erectile function.
