Involvement of metalloprotease-2 in the development of human brain microvessels.
The involvement of the metalloprotease-2 (MMP-2) in vessel development was investigated in the human telencephalon by double immunoreactions with antibodies to the enzyme, latent (proMMP-2) and active (aMMP-2) forms, and an antibody against collagen type IV, a constitutive component of the extracellular matrix (ECM) of the vessel basal lamina. MMP-2 is expressed in both 12- and 18-week telencephalic vessels, the proenzyme being mainly localised in endothelial cells and the active form prevailing in alpha-actin-reactive periendothelial cells identified as pericytes. Endothelial cells intensely positive for aMMP-2 were revealed in some microvessels and appeared locally associated with discontinuities of the collagen basal lamina. No detectable expression of MMP-2 was observed in perivascular glial processes revealed by vimentin/glial fibrillary acidic protein immunostainings. Double immunoreactions performed to further investigate telencephalon angiogenesis have demonstrated that both the endothelial cells and pericytes strongly express vascular endothelial growth factor (VEGF). Taken together, the results indicate that MMP-2 is largely involved in human brain angiogenesis and suggest that endothelial cells and pericytes tightly interplay in both angiogenesis mechanisms, by ECM proteolysis, and angiogenesis regulation, by local (autocrine/juxtacrine) VEGF action.
Girolamo
Francesco
F
Department of Human Anatomy and Histology, University of Bari School of Medicine, Italy.
Virgintino
Daniela
D
Errede
Mariella
M
Capobianco
Carmen
C
Bernardini
Nunzia
N
Bertossi
Mirella
M
Roncali
Luisa
L
D000199:Actins / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001812:Blood-Brain Barrier / Q000166:cytology / Q000196:embryology; D002454:Cell Differentiation; D004730:Endothelium, Vascular / Q000196:embryology / Q000201:enzymology*; D004792:Enzyme Precursors / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism*; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008666:Metalloendopeptidases / Q000378:metabolism*; D008833:Microcirculation / Q000196:embryology*; D013687:Telencephalon / Q000098:blood supply* / Q000196:embryology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D004792:Enzyme Precursors; D005904:Glial Fibrillary Acidic Protein; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase