Angiogenesis in autosomal-dominant polycystic kidney disease.
BACKGROUND
Autosomal-dominant polycystic kidney disease (ADPKD) is a genetic disorder that is responsible for approximately 10% of all cases of end-stage renal disease (ESRD). It is characterized by the formation of epithelial cell cysts, an increase in the extracellullar matrix, and vascular alterations believed to be the result of compression by the cysts. Our recent observations demonstrated a rich vascular network on the surface of the cysts, and thus, we postulated that angiogenesis could be a factor in the progression of ADPKD.


METHODS
Kidneys removed from patients with ADPKD were studied using (1) angiographs, (2) immunostaining [factor VIII-related antigen, vascular endothelial growth factor (VEGF), VEGF receptors 1 and 2 (VEGFR-1 and VEGFR-2), metalloproteinase-2 (MMP-2), and integrin alphavbeta3], and (3) Western blot analysis and enzyme-linked immunosorbent assay. The expression of VEGF165 in ADPKD cells in culture was determined.


RESULTS
There was (1) an extensive capillary network in the cyst wall of ADPKD kidneys, (2) morphological evidence of vascular malformations, (3) expression of VEGF165 in cyst cells of VEGFR-2 in endothelial cells and an absence of VEGFR-1 in endothelial cells, (4) secretion of VEGF165 by ADPKD cyst cells in culture, and (5) coexpression of matrix MMP-2 and integrin alphavbeta3 in vessels from ADPKD.


CONCLUSIONS
There is angiogenesis in ADPKD. This process may be necessary for cyst cells to grow and may be responsible for increased vascular permeability facilitating fluid secretion into the cysts. Neovascularization may result in the formation of aneurysms responsible for the renal bleeding in this disease.
Bello-Reuss
E
E
Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-0562, USA. ebellore@utmb.edu
Holubec
K
K
Rajaraman
S
S
D000792:Angiography; D001808:Blood Vessels / Q000473:pathology; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016891:Polycystic Kidney, Autosomal Dominant / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D019030:Receptors, Vitronectin / Q000378:metabolism; D012079:Renal Circulation; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D019030:Receptors, Vitronectin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D020778:Matrix Metalloproteinase 2