Smooth Muscle Origin of Cerebral Artery Balloon Cells in CADASIL: A Cerebral Small Vessel Disease
Greenstone, Nya E.
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Vascular dementia is the second most common form of dementia and usually occurs after multiple cerebral ischemic events. Although stroke and hypertension are strong acquired risk factors for both stroke and vascular dementia, this study focuses on the most common hereditary form of stroke and vascular dementia, Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leuokencephalopathy (CADASIL). CADASIL is caused by mutations affecting amino acid residues in NOTCH3 and is associated with large amounts of smooth muscle cell loss. This work addresses the cellular features of smooth muscle degeneration, which may lead to improved pathological detection of CADASIL. In addition to large amounts of vascular smooth muscle cell loss, some researchers have described an abnormally large type of cell known as “Balloon Cells” (BCs), in the arterial media of CADASIL patients. We first examined the specificity of BCs in CADASIL patients compared to control. Furthermore, previous studies have not characterized BCs in molecular detail. Therefore, we also tested the hypothesis that the BCs originate from smooth muscle by assessing for expression of canonical smooth muscle markers. Balloon cells were counted on each brain tissue section after being stained for various smooth muscle markers. The number of BCs per 100 vessels in CADASIL patients ranged from 0-58 compared to control patients with a range of 0-7. BCs also exhibited smooth muscle protein expression at a range of 6-100% by immunohistochemical analysis for TAGLN, CNN1, and PRKD3. In addition, in situ hybridization demonstrated the presence of smooth muscle mRNA in BCs. We conclude that BCs are significantly enriched in CADASIL vessels and that they are derived from smooth muscle cells. The results from this study may lead to the development of in vitro models, which may be useful for identification of treatments for CADASIL patients.
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