Characterization of VEGF and angiopoietins expression in human corpus cavernosum during aging.
OBJECTIVE
Erectile dysfunction (ED) is a highly prevalent and age-related disease, caused by endothelial dysfunction and impaired cavernous angiogenesis. However, cellular and molecular changes involved in erectile pathophysiology in aging male remain to be elucidated.


OBJECTIVE
To characterize the vascular organization, concomitantly with analysis of the expression of vascular endothelial growth factor (VEGF), Angiopoietin 1 (Ang1) and Angiopoietin 2 (Ang2) in young and aged human corpus cavernosum.


METHODS
Human penile fragments were removed from patients submitted to penile deviation surgery (11 cases; 58-70 years) and from potential organ donors (four cases; 18-28 years) without ED or risk factors for ED. Smooth muscle and connective tissue were assessed by Masson's trichrome staining and computer-assisted histomorphometry. Dual immunostaining for specific markers of endothelium (von Willebrand factor) and smooth muscle cell (alpha-actin), VEGF, Ang1 and Ang2 was assayed by fluorescence microscopy. Semi-quantification of expression of angiogenic factors was performed by Western blotting.


METHODS
Expression of VEGF and Angiopoietins in human corpus cavernosum, using a combination of histologic stainings, and molecular biology tools in order to achieve a better understanding of cavernosal tissue remodeling with aging.


RESULTS
Aged human corpus cavernosum presented wider sinusoidal spaces, loss of muscle cell bundles, and increased connective tissue content. Ang1 was scarcely expressed in small clusters in smooth muscle cell cytoplasm with identical localization in both studied groups. VEGF expression was abundant in smooth muscle cell and its expression markedly decreased in aged tissue, contrasting with the expression of angiopoietins that increased in the aged corpus cavernosum.


CONCLUSIONS
Immunoflourescent studies of cellular markers and growth factors help clarifying vascular organization and angiogenesis mechanisms in erectile tissue. Our findings demonstrate that the organization pattern of vascular endothelium and smooth muscle components of cavernosal tissue modifies during aging. Ang1 and Ang2 upregulation in human-aged penile tissue suggest a VEGF-independent vascular remodeling mechanism.
Tomada
Nuno
N
Department of Urology, Hospital de S. João, and Faculty of Medicine of Universidade do Porto, Portugal. nunotomada@gmail.com
Tomada
Inês
I
Cruz
Francisco
F
Vendeira
Pedro
P
Neves
Delminda
D
D000199:Actins / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D042683:Angiopoietin-1 / Q000032:analysis*; D042702:Angiopoietin-2 / Q000032:analysis*; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D018783:Impotence, Vasculogenic / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology; D010413:Penis / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D055815:Young Adult; D014841:von Willebrand Factor / Q000032:analysis
C467630:ANGPT1 protein, human; D000199:Actins; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor