Formation of new vasa vasorum in vasculitis - Production of angiogenic cytokines by multinucleated giant cells

Inflammation of the arterial wall in giant cell arteritis induces a series of structural changes, including the formation of new vasa vasorum. To stud y the regulation of neoangiogenesis in giant cell arteritis, temporal arter ies were examined for the extent and localization of microvessel generation and for the production of angiogenic factors. In normal arteries, vasa vas orum were restricted to the adventitia, but in inflamed arteries, capillari es emerged in the media and the intima. These capillaries displayed a disti nct topography with a circumferential arrangement in the external one-third of the intima. Neovascularization was closely correlated with the formatio n of lumen-obstructing intima, the fragmentation of the internal elastic la mina, and the presence of multinucleated giant cells. Comparison of tissue cytokine transcription in temporal arteries of giant cell arteritis patient s with and without up-regulated neoangiogenesis identified interferon-gamma and vascular endothelial growth factor but not fibroblast growth factor-2 as mediators associated with vasa vasorum proliferation. Giant cells and CD 68-positive macrophages at the media-intima junction were found to be the m ajor cellular sources of vascular endothelial growth factor. These data dem onstrate that formation of new vasa vasorum in vasculitis is regulated by i nflammatory cells and not by arterial wall cells, raising the possibility t hat it represents a primary disease mechanism and not a secondary hypoxia-i nduced event. Increased neovascularization in interferon-gamma-rich arterie s suggests that the formation of new vasa vasorum is determined by the natu re of the immune response in the arterial wall, possibly resulting from the generation and functional activity of multinucleated giant cells.