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Angiogenesis inhibitor endostatin is a distinct component of elastic fibers in vessel walls
Author(s) -
Miosge Nicolai,
Sasaki Takako,
Timpl Rupert
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.13.1743
Subject(s) - endostatin , immunogold labelling , colocalization , elastin , basement membrane , extracellular matrix , angiogenesis inhibitor , chemistry , decellularization , staining , collagenase , elastic fiber , angiogenesis , aorta , biophysics , microbiology and biotechnology , pathology , biology , anatomy , biochemistry , ultrastructure , enzyme , medicine , cancer research , cardiology
The endothelial cell inhibitor endostatin (22 kDa) is part of the carboxyl‐terminal globular domain of collagen XVIII and shows a widespread tissue distribution. Immunohistology of adult mouse tissues demonstrated a preferred localization in many vessel walls and some other basement membrane zones. A strong immunogold staining was observed across elastic fibers in the multiple elastic membranes of aorta and other large arteries. Staining was less strong along sparse elastic fibers of veins and almost none was observed in the walls of arte‐rioles and capillaries. Strong evidence was also obtained for some intracellular and basement membrane associations. Immunogold double staining of elastic fibers showed a close colocalization of endostatin with fibulin‐2, fibulin‐1, and nidogen‐2, but not with perlecan. Reasonable amounts of endosta‐tin could be extracted from aorta and skin by EDTA, followed by detergents, with aorta being the richest source of the inhibitor identified so far. Solubilizations with collagenase and elastase were ∼fivefold less efficient. Immunoblots of aortic extracts detected major endostatin components of 22–25 kDa whereas skin extracts also contained some larger components. Solid‐phase assays demonstrated distinct binding of recombinant mouse endostatin to the fibulins and nidogen‐2, consistent with their tissue colocalization. Together, the data indicate several different ways for endostatin to be associated with the extracellular matrix, and its release may determine biological activation. This also defines a novel function for some elastic tissues.—Miosge, N., Sasaki, T., Timpl, R. Angiogenesis inhibitor endosta‐tin is a distinct component of elastic fibers in vessel walls. FASEB J . 13, 1743–1750 (1999)