Erectile dysfunction precedes other systemic vascular diseases due to incompetent cavernous endothelial cell-cell junctions.
PURPOSE
Erectile dysfunction is often a harbinger of cardiovascular disease. We sought to gain mechanistic insight at the cellular and molecular levels into why erectile dysfunction precedes the clinical consequences of cardiovascular disease.


MATERIALS AND METHODS
Diabetes was induced by intraperitoneal streptozotocin injection in 8-week-old C57BL/6J mice. At 8 weeks after diabetes induction, we determined the expression of endothelial cell-cell junction proteins and vascular endothelial permeability in the penis, heart and hind limb by systemic injection of various vascular space markers (350 Da to 2,000 kDa) or by immunohistochemical staining with antibody to oxidized low density lipoprotein. We also investigated the effect of recombinant Ang1 protein on cavernous endothelial permeability.


RESULTS
Alterations in the integrity of the endothelial cell-cell junction, including a decrease in endothelial cell-cell junction proteins and an increase in vascular permeability to fluorescent tracers or oxidized low density lipoprotein, were prominent in the cavernous tissue of diabetic mice. In contrast, no significant changes in endothelial cell-cell junction proteins or vascular permeability were noted in heart or hind limb tissue according to the diabetic condition. Intracavernous injection of Ang1 protein, an anti-permeability factor, significantly decreased cavernous endothelial permeability to oxidized low density lipoprotein by restoring endothelial cell-cell junction proteins in diabetic mice.


CONCLUSIONS
The incompetent cavernous endothelial cell-cell junction in the diabetic condition provides an important clue to why erectile dysfunction is highly prevalent and often precedes other systemic vascular diseases.
['Ryu|Ji-Kan|JK|', 'Jin|Hai-Rong|HR|', 'Yin|Guo Nan|GN|', 'Kwon|Mi-Hye|MH|', 'Song|Kang-Moon|KM|', 'Choi|Min Ji|MJ|', 'Park|Jin-Mi|JM|', 'Das|Nando Dulal|ND|', 'Kwon|Ki-Dong|KD|', 'Batbold|Dulguun|D|', 'Lee|Tack|T|', 'Gao|Zhen Li|ZL|', 'Kim|Kyu-Won|KW|', 'Kim|Woo Jean|WJ|', 'Suh|Jun-Kyu|JK|']
D000704:Analysis of Variance D042683:Angiopoietin-1 D000818:Animals D015153:Blotting, Western D002318:Cardiovascular Diseases D003326:Coronary Circulation D003921:Diabetes Mellitus, Experimental D004730:Endothelium, Vascular D007172:Erectile Dysfunction D006614:Hindlimb D007365:Intercellular Junctions D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D010413:Penis D018709:Statistics, Nonparametric
erectile dysfunction endothelial cell-cell cardiovascular disease cardiovascular disease vascular endothelial penis low density lipoprotein Ang1 NO CVD EC ED HUVEC ICP LDL MCEC PECAM-1 VE ZO-1 angiopoietin-1 cardiovascular diseases diabetes mellitus human umbilical vein endothelial cell intracavernous pressure intracellular junctions mouse cavernous endothelial cell nitric oxide platelet/endothelial cell adhesion molecule-1 zonular occludens-1