Tässä on tosiaan pohdittavaa moneksi päiväksi.
Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead
Abstract
Sprouting angiogenesis is an invasive
process that involves proteolytic activities required for the
degradation of the endothelial
basement membrane, cell migration with removal of
obstructing matrix proteins, and generation of space in the matrix to
allow
endothelial cells to form a proper lumen.
In the
last decade it has become clear that besides these matrix-degrading
properties,
proteases exert additional, more subtle functions
that play a key role in angiogenesis. These functions are discussed with
specific emphasis on membrane type-1 matrix
metalloproteinase (MT1-MMP), other MMPs, and the related ADAMs (a
disintegrin
and metalloproteinase domain).
Proteases modulate
the balance between pro- and anti-angiogenic factors by activation and
modification
of growth factors and chemokines, ectodomain
shedding with accompanied receptor activation, shedding of cytokines
from membrane-bound
precursors, and generation of (matrix) protein
fragments that inhibit or activate angiogenesis.
Furthermore, they
participate
in the recruitment of leukocytes and progenitor
cells, which contribute to the onset and progression of angiogenesis.
Proteases
facilitate the mobilization of progenitor cells in
the bone marrow as well as the entry of these cells and leukocytes into
the angiogenic area.
The interaction between
pericytes and the newly formed endothelial tubes is accompanied by
silencing
of MMP activities.
Better understanding of the
various activities of proteases may be helpful in developing more
specific
inhibitors that could result in tailor-made
modification of proteolytic activities in disease.
