Type IV collagen modulates angiogenesis and neovessel survival in the rat aorta model

Type IV collagen is a major basement membrane component that has been impli cated in the regulation of angiogenesis. The purpose of this study was to e valuate the effect of type IV collagen an the angiogenic response of native endothelial cells in three-dimensional vascular organ culture. Rings of ra t aorta were cultured under serum-free conditions in gels of type I collage n with or without type IV collagen. In the absence of type IV collagen, aor tic rings generated neovessels, which proliferated until day 9 and graduall y regressed during the second and third weeks of culture. Type IV collagen promoted neovessel elongation and survival in a dose-dependent manner. Micr ovascular length increased by 43, 57, and 119% over control values in cultu res treated with 3, 30, and 300 mu g/ml type IV collagen, respectively. Whe n used at high concentrations (300 mu g/ml) type TV collagen stabilized the neovascular outgrowths and prevented vascular regression. Type IV collagen also promoted the formation of neovessels, but significant stimulatory eff ects were observed only at an intermediate concentration (30 mu g/ml) and w ere no longer significant at the high concentration (300 mu g/ml). The obse rvation that type IV collagen has dose-dependent effects on vascular elonga tion, proliferation, and stabilization, supports the concept that the devel oping basement membrane of neovessels acts as a solid-phase regulator of an giogenesis, whose function varies depending on the concentration of its mol ecular components.