Three-dimensional, quantitative analysis of desmin and smooth muscle alpha actin expression during angiogenesis

Angiogenic therapies have been designed for many pathological conditions, but when used as a single therapy, the clinical results have fallen short of expectations. In addition, strategies for vascularizing engineered tissues have been unsuccessful in promoting the formation of an extensive, stable vasculature. Recent evidence suggests that mural cells play a critical role in the success of these approaches, but our current understanding of the function of mural cells in the microvasculature is incomplete. We studied the three-dimensional spatial and temporal kinetics of the mural cell markers desmin and smooth muscle alpha actin during angiogenesis in an in vivo fibrin gel model. The results led to the following conclusions: (1) desmin and smooth muscle alpha actin positive cells are present during the initial development of vessel sprouts; (2) the presence of these cells in the microvasculature is not always an indicator of vessel stability; and (3) the mural cell markers desmin and smooth muscle alpha actin exhibit differential staining patterns during vessel formation. These findings shed new light on the complexity of the relationship between mural cells and the formation of a mature, stable microcirculation.