Pericytes as a new target for pathological processes in CADASIL
Article first published online: 12 JAN 2012
© 2012 Japanese Society of Neuropathology
Volume 32, Issue 5, pages 515–521, October 2012
How to Cite
Dziewulska, D. and Lewandowska, E. (2012), Pericytes as a new target for pathological processes in CADASIL. Neuropathology, 32: 515–521. doi: 10.1111/j.1440-1789.2011.01290.x
- Issue published online: 23 SEP 2012
- Article first published online: 12 JAN 2012
- Received 3 July 2011; revised 4 December 2011 and accepted 7 December 2011; published online 12 January 2012.
- capillary vessels;
- Notch 3;
- white matter
CADASIL is a generalized angiopathy caused by mutations in NOTCH 3 gene leading to degeneration and loss of vascular smooth muscle cells (VSMC) in small arteries and arterioles. Since the receptor protein encoded by NOTCH 3 gene is expressed not only on VSMC but also on pericytes, pericytes and capillary vessels can be damaged by CADASIL. To check this hypothesis we examined microvessels in autopsy brains and skin-muscle biopsies of CADASIL patients. We found degeneration and loss of pericytes in capillary vessels. Pericytes were shrunken and their cytoplasm contained numerous vacuoles, big vesicular structures and complexes of enlarged pathological mitochondria. Degenerative changes were also observed within endothelial-pericytic connections, especially within peg-and-socket junctions. Nearby pericyte cell membranes or inside infoldings, deposits of granular osmiophilic material (GOM) were usually seen. In the affected capillaries endothelial cells revealed features of degeneration, selective death or swelling, leading to narrowing or occlusion of the capillary lumen. Our findings indicate that in CADASIL not only VSMC but also pericytes are severely damaged. Pericyte involvement in CADASIL can result in increased permeability of capillary vessels and disturbances in cerebral microcirculation, leading to white matter injury. Since in capillaries pericytes regulate vessel contractility, their degeneration can also cause defective vasomotor reactivity, the phenomenon observed very early in CADASIL, before development of histopathological changes in vessel walls.