In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 94, No. 4 ( 2004-03-05), p. 462-470
Kurzfassung:
We examined the function of α 4 β 1 integrin in angiogenesis and in mediating endothelial cell responses to the angiogenesis modulators, thrombospondin-1 and thrombospondin-2. α 4 β 1 supports adhesion of venous endothelial cells but not of microvascular endothelial cells on immobilized thrombospondin-1, vascular cell adhesion molecule-1, or recombinant N-terminal regions of thrombospondin-1 and thrombospondin-2. Chemotactic activities of this region of thrombospondin-1 and thrombospondin-2 are also mediated by α 4 β 1 , whereas antagonism of fibroblast growth factor-2–stimulated chemotaxis is not mediated by this region. Immobilized N-terminal regions of thrombospondin-1 and thrombospondin-2 promote endothelial cell survival and proliferation in an α 4 β 1 -dependent manner. Soluble α 4 β 1 antagonists inhibit angiogenesis in the chick chorioallantoic membrane and neovascularization of mouse muscle explants. The latter inhibition is thrombospondin-1–dependent and not observed in explants from thrombospondin-1 −/− mice. Antagonizing α 4 β 1 may in part block proangiogenic activities of thrombospondin-1 and thrombospondin-2, because N-terminal regions of thrombospondin-1 and thrombospondin-2 containing the α 4 β 1 binding sequence stimulate angiogenesis in vivo. Therefore, α 4 β 1 is an important endothelial cell receptor for mediating motility and proliferative responses to thrombospondins and for modulation of angiogenesis.
Materialart:
Online-Ressource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.0000115555.05668.93
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2004
ZDB Id:
1467838-X
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