Endothelial changes in muscle and skin biopsies in patients with CADASIL

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is characterized by the deposition of granular osmiophilic material in association with vascular smooth muscle cells in many different organs. However, the cause of the subsequent destruction of smooth muscle cells that are surrounded by granular osmiophilic material is unclear. In the present study, the ultrastructural changes that occur in endothelial cells in CADASIL have been evaluated by examining blood vessels in six skin biopsies and seven muscle biopsies belonging to three different CADASIL pedigrees. The appearances have been compared with five 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 attenuation of endothelial cells and increased density of endothelial cytoplasm, accompanied by the presence of compact bundles of microfilaments within the cytoplasm of endothelial cells. Endothelial cells in muscle biopsies from CADASIL patients, on the other hand, were swollen until destruction of tight junctions were observed. These findings suggest that impaired permeability of vascular endothelium may play a role in the destruction of vascular smooth muscle cells in CADASIL. Furthermore, the results of this study suggest that further fine structural investigation of blood vessel endothelium and underlying smooth muscle may lead to a better understanding of the pathophysiology of CADASIL.

Blood vessel ultrastructural picture in a CADASIL patient diagnosed at an advanced age

“…Endothelial cells in our material exhibited changes similar to those previously described in CADASIL patients [2,23].…”

Physiology and pathology of notch signalling system

“…In fact, endothelial cells in muscle and skin biopsies of CADASIL patients also show abnormalities, particularly in tight and gap junctions (Ruchoux and Maurage, 1998). These changes, evident in CADASIL patients, were attributed to loss of VSMC (Brulin et al, 2002).…”

Bone Marrow-Derived Progenitor Cells in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

“…Although the disease pathology affects mainly the tunica media, endothelial changes, including cytoplasmic swelling, disruption of tight junctions, and appearance of bundles of microfilaments, have been also reported. 36 Altered endothelial-dependent vasodilatation in cerebral and forearm arteries and higher levels of asymmetrical dimethylarginine, a nitric oxide endogenous inhibitor, have been found. 14,15,37 Even if our findings support the involvement of the endothelium in the pathogenesis of the disease, differently from the experimental setting, in vivo studies do not allow to establish whether this is associated with a failure of angiogenesis.…”