Vasohibin-1 rescues erectile function through up-regulation of angiogenic factors in the diabetic mice

Sci Rep. 2021 Jan 13;11(1):1114. doi: 10.1038/s41598-020-80925-7.

Abstract

Neovascularization of the erectile tissue emerges as a beneficial curative approach to treat erectile dysfunction (ED). Here we for the first time report the unexpected role of vasohibin-1 (VASH1), mainly known as an anti-angiogenic factor, in restoring erectile function in diabetic mice. A diabetic patient has lower cavernous VASH1 expression than in the potent man. VASH1 was mainly expressed in endothelial cells. There were significant decreases in cavernous endothelial cell and pericyte contents in VASH1 knockout mice compared with those in wild-type mice, which resulted in impairments in erectile function. Intracavernous injection of VASH1 protein successfully restored erectile function in the diabetic mice (~ 90% of control values). VASH1 protein reinstated endothelial cells, pericytes, and endothelial cell-cell junction proteins and induced phosphorylation of eNOS (Ser1177) in the diabetic mice. The induction of angiogenic factors, such as angiopoietin-1 and vascular endothelial growth factor, is responsible for cavernous angiogenesis and the restoration of erectile function mediated by VASH1. Altogether, these findings suggest that VASH1 is proangiogenic in diabetic penis and is a new potential target for diabetic ED.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-1 / antagonists & inhibitors
  • Angiopoietin-1 / metabolism
  • Animals
  • Cell Cycle Proteins / administration & dosage
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle Proteins / therapeutic use*
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / metabolism
  • Down-Regulation
  • Endothelial Cells / physiology
  • Erectile Dysfunction / drug therapy*
  • Erectile Dysfunction / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic
  • Nitric Oxide Synthase Type III / metabolism
  • Penile Erection*
  • Penis / blood supply
  • Penis / metabolism*
  • Pericytes / physiology
  • Phosphorylation
  • Tight Junction Proteins / metabolism
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiopoietin-1
  • Angpt1 protein, mouse
  • Cell Cycle Proteins
  • Tight Junction Proteins
  • Vascular Endothelial Growth Factor A
  • Vash1 protein, mouse
  • vascular endothelial growth factor A, mouse
  • Nitric Oxide Synthase Type III