Capillary vessel wall in CADASIL angiopathy

• Published in: Folia neuropathologica Vol. 48; no. 2; pp. 104 - 115
• Main Authors: Lewandowska, Eliza, Szpak, Grazyna M, Wierzba-Bobrowicz, Teresa, Modzelewska, Joanna, Stepień, Tomasz, Pasennik, Elzbieta, Schmidt-Sidor, Bogna, Rafałowska, Janina
• Format: Journal Article
• Language: English
• Published: Poland 2010
• Subjects: Adult; CADASIL - pathology; Capillaries - ultrastructure; Endothelium, Vascular - ultrastructure; Humans; Immunohistochemistry; Microscopy, Electron, Transmission; Middle Aged; Muscle, Smooth, Vascular - ultrastructure; Pericytes - ultrastructure
• ISSN: 1641-4640; 1509-572X

The study was aimed at investigating the morphology of capillaries in four skin and muscle biopsy specimens obtained from CADASIL patients. In all cases diagnosis confirmed at the ultrastructural level, and additionally in three cases, the genetic test revealed the Notch3 gene mutations. Using histological and immunohistochemical (IHC) markers for components of capillary vessel wall we showed the reduction and loss of pericytes and and fibrous vessel wall including the thickened basement membrane. The thorough ultrastructural study revealed the presence of widespread GOM deposits in capillary wall, but less numerous than in arterioles. They were located in the vicinity of pericytes and also in pericyte infolding like vascular smooth muscle cells (VSMC) in arterioles. Sometimes GOM deposits were observed near endothelial cells. The endothelial cells, damaged but not lost, were also observed while most of capillaries revealed only residual pericytes. The destruction and loss of pericytes in capillary wall, like those of VSMC in arteriole wall, was the main vascular pathology in our the examined cases consistent to that pericytes functionally correspondent to VSMC. The Notch3 receptor is expressed on VSMC and pericytes, the results of our study confirm that in capillaries devoid of VSMC, pericytes are the primary morphological target of the Notch3 gene mutation. It should be indicated that in diagnostic ultrastructural examinations of skin and/or skeletal muscle biopsies, not only arterioles but also capillaries, occurring in a larger amount, should be thoroughly analysed, because such an approach may facilitate the detection of GOM deposits - the pathognomonic feature of CADASIL.