First Author | Woodman SE | Year | 2003 |
Journal | Am J Pathol | Volume | 162 |
Issue | 6 | Pages | 2059-68 |
PubMed ID | 12759260 | Mgi Jnum | J:109484 |
Mgi Id | MGI:3629009 | Doi | 10.1016/S0002-9440(10)64337-4 |
Citation | Woodman SE, et al. (2003) Caveolin-1 knockout mice show an impaired angiogenic response to exogenous stimuli. Am J Pathol 162(6):2059-68 |
abstractText | Recent studies have shown that caveolin-1 (Cav-1) plays an important role as a regulator of angiogenesis in vitro. Here, we use Cav-1 knockout (KO) mice as a model system to examine the in vivo relevance of these findings. A primary mediator of angiogenesis is basic fibroblast growth factor (bFGF). Thus, we studied bFGF-induced angiogenesis in Cav-1 KO mice using a reconstituted basement membrane system, ie, Matrigel plugs, supplemented with bFGF. In Cav-1 KO mice, implanted Matrigel plugs showed a dramatic reduction in both vessel infiltration and density, as compared with identical plugs implanted in wild-type control mice. We also examined the necessity of Cav-1 to support the angiogenic response of an exogenous tumor by subcutaneously injecting Cav-1 KO mice with the melanoma cell line, B16-F10. We show that tumor weight, volume, and vessel density are all reduced in Cav-1 KO mice, consistent with diminished angiogenesis. Ultrastructural analysis of newly formed capillaries within the exogenous tumors reveals a lack of endothelial caveolae and incomplete capillary formation in Cav-1 KO mice. These results provide novel evidence that Cav-1 and caveolae play an important positive role in the process of pathological angiogenesis in vivo. |