Aortic rings stimulate inflammatory angiogenesis in a subcutaneous implant in vivo model

Rat or mouse aortic rings produce angiogenic outgrowths in vitro through endogenous production of growth factors and inflammatory cytokines. To further investigate this process in vivo, collagen-Gelfoam constructs containing aortic rings were implanted subcutaneously in syngeneic animals. Aortic rings stimulated a prominent angiogenic response characterized by peri- and intra-aortic accumulation of florid granulation tissue. Conversely, implants without rings elicited a non-specific inflammatory reaction without significant angiogenesis. The angiogenic response to the rings peaked at day 14 and was followed by regression of neovessels, which were mostly reabsorbed by day 28. Gene expression studies showed upregulated expression of angiogenic growth factors and cytokines in implants with rings. Tracking experiments with LacZ expressing ROSA26 transgenic mice demonstrated that both the aorta and the host contributed to the angiogenic response. These studies show that the angiogenic properties of the rodent aorta can be studied in the live animal under conditions that can be monitored and quantified. This in vivo assay can be used to study the molecular mechanisms by which the arterial wall and its proangiogenic cytokines regulate formation of granulation tissue during wound healing.