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Published on: January 12, 2020
Involvement of metalloprotease-2 in the development of human brain microvessels
Francesco Girolamo1, Daniela Virgintino, Mariella Errede
1Department of Human Anatomy and Histology, University of Bari School of Medicine, Italy.
Abstract:
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.
Insights
Metalloprotease-2 (MMP-2) plays a key role in human brain vessel development. Endothelial cells and pericytes interact via MMP-2 and VEGF, influencing angiogenesis and extracellular matrix remodeling.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Vessel development, or angiogenesis, is crucial for brain formation.
- Metalloprotease-2 (MMP-2) is implicated in extracellular matrix remodeling, a key process in angiogenesis.
Purpose of the Study:
- To investigate the role of MMP-2 in human telencephalon angiogenesis.
- To identify the cellular localization of MMP-2 and its relationship with collagen type IV and vascular endothelial growth factor (VEGF).
Main Methods:
- Double immunohistochemistry was used to detect MMP-2 (latent and active forms), collagen type IV, and VEGF in human telencephalon tissue.
- Immunostaining for vimentin/glial fibrillary acidic protein identified glial processes.
Main Results:
- MMP-2 was expressed in 12- and 18-week telencephalic vessels, with the proenzyme in endothelial cells and the active form in pericytes.
- Active MMP-2 in endothelial cells was associated with basal lamina discontinuities.
- Both endothelial cells and pericytes expressed VEGF, suggesting a coordinated role in angiogenesis.
Conclusions:
- MMP-2 is significantly involved in human brain angiogenesis.
- Endothelial cells and pericytes engage in a complex interplay, utilizing MMP-2 for extracellular matrix proteolysis and VEGF for angiogenesis regulation.
