EXPRESSION OF ANGIOGENIC FACTORS AND STRUCTURAL PROTEINS IN CENTRAL-NERVOUS-SYSTEM VASCULAR MALFORMATIONS

LITTLE IS KNOWN of the molecular mechanisms mediating the genesis and subsequent biological behavior of central nervous system vascular malf ormations. The role of angiogenic and permeability-inducing factors in the pathogenesis of these lesions has not been previously explored. I n this study, we subject specimens from 12 cases of excised vascular m alformation to a battery of immunostaining for vascular endothelial gr owth factor, basic fibroblast growth factor, and selected structural a nd matrix proteins. The lesions consisted of seven arteriovenous malfo rmations (AVMs), including one angiographically occult AVM, one arteri alized vein from a dural AVM, and five cavernous malformations (CMs). Vascular endothelial growth factor was expressed by all lesions and wa s localized predominantly in the subendothelial layer and in perivascu lar spaces. Four of seven AVMs and four of five CMs demonstrated faint basic fibroblast growth factor expression that was localized to the m edia of AVM vessels and the subendothelial layer and intercavernous ma trix of CMs. This pattern of angiogenic factor immunostaining was corr elated with the expression of structural and matrix proteins in the sa me lesions. Laminin was not expressed in any of the CMs, confirming pr evious reports from our laboratory. By contrast, fibronectin expressio n was more prominent in CMs than in AVMs. Collagen Type IV and alpha s mooth muscle actin expression occurred in every lesion. We conclude th at angiogenic growth factors are expressed in all types of vascular ma lformations of the central nervous system. The pattern of expression s uggests diffuse activation of angiogenesis without specific relation t o individual vessel types or recent clinical behavior. Defining the ro le of angiogenesis in vascular malformations might provide insight int o their pathogenesis and suggest novel strategies for modification of their behavior.