Large-vessel endothelium switches to a microvascular phenotype during angiogenesis in collagen gel culture of rat aorta.

The purpose of this study was to investigate the vasoformative behavior in vitro of the native intimal endothelium of the rat aorta. To visualize the intimal surface directly, thoracic aortas were everted using a procedure that sequestered adventitial cells and possible remnant microvessels of periaortic soft tissues inside the aortic tube. Everted aortas embedded in collagen gel and cultured under serum-free conditions generated branching microvessels by a process of sprouting from the aortic intima. The newly formed microvessels originated from patches of activated intimal endothelial cells, which had survived the mechanical damage of the eversion procedure. Activated endothelial cells crawled over each other and engaged in lumen formation forming bilayers or multilayers of cells which became the source of sprouting histotypic microvessels. The endothelium of the newly formed microvessels was positive for factor VIII-related antigen and was partially surrounded by periendothelial cells which expressed alpha-smooth muscle actin. The results of this study indicate that the intimal endothelium of the rat aorta has considerable functional plasticity and can switch to a vasoformative phenotype in response to changes in the surrounding extracellular matrix environment.