Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing

Abstract

Previous in vivo and in vitro studies have shown that Akt1 serves as a crucial regulator of vascular maturation, extracellular matrix composition, and angiogenesis in tumors. Hence, we hypothesized that Akt1 may be necessary for other angiogenesis-dependent processes, including wound healing. Using Akt1 ^−/− and Akt2 ^−/− mice, we demonstrate that deficiency of Akt1, but not Akt2, results in impaired assembly of collagen in skin wounds and around the blood vessels. Wounds in Akt1 ^−/− mice, but not in Akt2 ^−/− mice, were characterized by reduced vascular area as well as impaired vascular maturation as evidenced by reduced smooth muscle cell recruitment. Expression level of a major angiogenic growth factor, VEGF, was significantly lower in wound tissues of Akt1 ^−/− mice as compared to WT. However, despite the impaired collagen assembly and reduced angiogenesis in Akt1 ^−/− wounds, no significant difference in migration of fibroblasts into the wound area was observed between WT and Akt1 ^−/− mice. Importantly, the dynamics of wound closure were similar between WT, Akt1 ^−/−, and Akt2 ^−/− mice. Thus, it appears that although the lack of Akt1 impairs VEGF expression, wound angiogenesis, and subsequent maturation of vasculature, it has no effect on the wound closure. These findings may have clinical applications for the improvement of treatment procedures with reported history of wound healing complications.