Abstract WP282: Gender-Dependent Differences in the Cerebrovascular System in Wildtype Mice and Cerebrovascular Lesions in a Mouse Model of Moyamoya Disease

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Mutations in ACTA2 predispose to a spectrum of vascular diseases, including Moyamoya-like cerebrovascular disease (MMD). Acta2-/- mice show straightening of cerebral arteries, narrowing and occlusions characteristic of MMD. They do not show typical MMD collaterals, but exhibit thick bypasses, perfusing ischemic zones. We found a set of altered morphological parameters with females exhibiting the most advanced vascular alterations.Methods: Animals (n=12) at 7 wk age were injected with liposomal blood pool CT contrast agent, average particle size 130 nm, iodine concentration 2.2 mg/g and imaged immediately with μ-CT. Individual scan time was ~50 min. Detailed morphometric analysis of Circle of Willis (CoW) territory was performed.Results:Acta2+/+ males and females do not show significant differences for morphometric features associated with MMD. Knockout animals Acta2-/- exhibit several morphometric changes compared to wild type. Acta2-/- females revealed the greatest severity of cerebral malformation in the narrowing of L-SCA, curvature and mean circularity of L-ITCD and the smallest CoW area.Conclusion:Acta2-/- animals show straightening of large cerebral arteries and narrowing, characteristic features of MMD, Acta2-/- females have more prominent malformations compared to males, as in the human patients. Results of this study may help in better understanding the complexity of MMD and shed light on possibilities for new therapy development.

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