Caveolin-1 Knockout Mice Show an Impaired Angiogenic Response to Exogenous Stimuli

Am J Pathol. 2003 Jun;162(6):2059-68. doi: 10.1016/S0002-9440(10)64337-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Capillaries / pathology
  • Capillaries / ultrastructure
  • Caveolae / pathology
  • Caveolae / ultrastructure
  • Caveolin 1
  • Caveolin 2
  • Caveolins / genetics*
  • Caveolins / metabolism
  • Collagen
  • Drug Combinations
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / ultrastructure
  • Fibroblast Growth Factor 2 / pharmacology*
  • Genotype
  • Laminin
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal / methods
  • Microscopy, Electron
  • Neoplasm Transplantation
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / prevention & control
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / prevention & control
  • Neovascularization, Physiologic / drug effects*
  • Proteoglycans
  • Tumor Cells, Cultured

Substances

  • Cav1 protein, mouse
  • Caveolin 1
  • Caveolin 2
  • Caveolins
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • Fibroblast Growth Factor 2
  • matrigel
  • Collagen