Abstract 561: Micro-CT Visualizes Extensive Vascular Pathologies In Smooth Muscle Cell-specific LRP1 Deficient Mice

Objective: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional protein that is abundant in vascular smooth muscle cells (SMCs). SMC-specific deletion of LRP1 leads to vascular pathologies in the aorta and superior mesenteric artery (SMA) of mice. Although other vascular beds have not been explored. Micro-computed tomography (CT) enables scanning in a high spatial resolution (~20 μm). To determine the regional effects of SMC-specific LRP1 deficiency in mice, we performed detailed morphometric analyses of vascular pathologies using micro-CT. Approach and Results: Male and female wild-type and SMC-specific LRP1 deficient mice were monitored for aortic and SMA dilatations from 6 weeks through 40 weeks of age using ultrasonography. Progressive luminal dilatations of the ascending aorta were detected in both male and female SMC-specific LRP1 deficient mice, compared to their wild type littermates. Ultrasound was only able to detect the superior mesenteric artery within ~2 mm of the branch from the abdominal aorta. Therefore, ultrasonography is not optimal for monitoring the SMA. At the age of 40 weeks, mice were euthanized, perfused with saline and injected with Microfil silicone rubber through the left ventricle. Subsequently, each mouse was scanned by a Bruker SkyScan 1276 high-resolution desktop micro-CT and 3 dimensional images were generated. Aortic CT images showed profound dilatations of the entire aorta and its main branches, with more pronounced changes in the ascending thoracic and infrarenal aortic regions. Micro-CT also detected longer and tortuous aortic structure, compared to their wild type littermates. The most striking pathologies, including both dilation and tortuosity, were observed in the SMA and its branches with more depth and detailed insights, compared to ultrasonography. Conclusions: The ability to visualize the entire vasculature of mice using micro-CT technology demonstrated that SMC-specific deficiency of LRP1 has marked heterogeneity in development of vascular pathologies.