Increased endothelial apoptotic cell density in human diabetic erectile tissue--comparison with clinical data.
BACKGROUND
Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum.


OBJECTIVE
To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status.


METHODS
Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT).


METHODS
Establish an index of ACD and correlate those results with patient clinical data.


RESULTS
Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 +/- 0.44 (mean apoptotic cells/tissue area mm(2) +/- standard error). The diabetic group showed an increased ACD of 23.82 +/- 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI.


CONCLUSIONS
We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI.
Costa
Carla
C
Laboratory for Molecular Cell Biology, Faculty of Medicine of the University of Porto, Porto, Portugal.
Soares
Raquel
R
Castela
Angela
A
Adães
Sara
S
Hastert
Véronique
V
Vendeira
Pedro
P
Virag
Ronald
R
D017209:Apoptosis / Q000502:physiology*; D002452:Cell Count; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D004730:Endothelium, Vascular / Q000473:pathology*; D007172:Erectile Dysfunction / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D018783:Impotence, Vasculogenic / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology; D010413:Penis / Q000187:drug effects; D011788:Quality of Life / Q000523:psychology; D012307:Risk Factors; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D009569:Nitric Oxide