Jg. Pickering et al., alpha 5 beta 1 integrin expression and luminal edge fibronectin matrix assembly by smooth muscle cells after arterial injury, AM J PATH, 156(2), 2000, pp. 453-465
Citations number
44
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Fibronectin is secreted from the cell as a soluble protein that must then p
olymerize to regulate cell function. To elucidate the process of fibronecti
n matrix assembly in vascular disease, we immunostained sections of balloon
-injured rat carotid artery for the fibronectin-binding alpha 5 beta 1 inte
grin. Whereas alpha 5 beta 1 integrin was not evident in the normal carotid
artery, its expression was induced after a vascular injury. By 14 days, th
e alpha 5 beta 1 integrin was localized exclusively to the less differentia
ted smooth muscle cells (SMCs) at the luminal surface of the neointima. Pla
telet-derived growth factor-BB, dominant in neointimal formation, selective
ly increased the expression of the alpha 5 beta 1 integrin by human SMCs in
culture. To track the assembly of fibronectin fibers, fluorescence-labeled
soluble fibronectin protomers were added to cultured SMCs and to fresh seg
ments of normal and balloon-injured rat carotid arteries. Fibronectin fiber
formation in cultured SMCs could be detected within 10 minutes, and was bl
ocked by an RGD peptide, an anti-beta 1 integrin antibody, and an anti-alph
a 5 beta 1 integrin antibody, but not by an anti-beta 3 integrin antibody.
En face confocal microscopy of arterial segments revealed that soluble fibr
onectin had polymerized on the alpha 5 beta 1 integrin-expressing SMCs of t
he luminal surface of the injured arterial neointima, but not on the alpha
5 beta 1 integrin-negative neointimal SMCs below this or on the endothelial
cells of uninjured arteries. Furthermore, in situ fibronectin assembly by
the neointimal SMCs was inhibited by an RGD peptide and by an anti-beta 1 i
ntegrin antibody. These studies indicate that a subpopulation of SMCs in th
e repairing artery wall orchestrates integrin-mediated fibronectin assembly
.