ENDOTHELIAL CHANGES IN MUSCLE AND SKIN BIOPSIES IN PATIENTS WITH CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is characterized by the deposition of g ranular osmiophilic material in association with vascular smooth muscl e cells in many different organs. However, the cause of the subsequent destruction of smooth muscle cells that are surrounded by granular os miophilic material is unclear. In the present study, the ultrastructur al changes that occur in endothelial cells in CADASIL have been evalua ted by examining blood vessels in sire skin biopsies and seven muscle biopsies belonging to three different CADASIL pedigrees. The appearanc es have been compared with ave skin biopsies and five muscle biopsies from age-matched controls without vascular disease, The most striking features observed in vessels in the skin of CADASIL patients were atte nuation of endothelial cells and increased density of endothelial cyto plasm, accompanied by the presence of compact bundles of microfilament s within the cytoplasm of endothelial cells. Endothelial cells in musc le biopsies from CADASIL patients, on the other hand, were swollen unt il destruction of tight junctions were observed. These findings sugges t that impaired permeability of vascular endothelium may play a role i n the destruction of vascular smooth muscle cells in CADASIL. Furtherm ore, the results of this study suggest that further fine structural in vestigation of blood vessel endothelium and underlying smooth muscle m ay lead to a better understanding of the pathophysiology of CADASIL.