Notch3 gene mutation results in hypoplasia of arterial smooth muscle cells

Abstract

Objective To describe the changes of cell development associated contracture and structure proteins in vascular smooth muscle cells (VSMCs) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods The clinical manifestation of probands in 6 families showed the recurrent cerebral ischemic event. A part of patients showed dementia. The genetic analysis in all probands showed Notch3 gene mutation. All probands received the sural nerve biopsy. The primary antibodies against α-smooth muscle actin, smooth muscle myosin heavy chain, desmin and vimenfin were used in immunohistochemistry staining on all of them. Results VSMCs showed hypertrophy or atrophy in the arterioles with different caliber. The granular osmiophilic material (GOM) could be found within the basal lamina of arteriole VSMCs in all of the probands. The expressions of α-smooth muscle actin and smooth muscle myosin heavy chain were partly lost, negative or unevenly distributed in the VSMCs in the arteriole. The expression of desmin showed also unregular distribution or partial loss. The expression of vimentin was partly enhanced. Conclusions The VSMCs show the physiological features of synthetic configuration, indicating the hypoplasia of VSMCs in the arterioles of CADASIL. The VSMCs of the larger arteriole were more severely involved. Key words: CADASIL; Muscle, smooth, vascular; Sural nerve; Receptors, notch