Novel Techniques for Vascular Investigation

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

Over the last year, weve continued to both fold in existing vascular physiology techniques and to leverage the newly optimized methodology for latex casting of organ-based vasculature into several projects. These techniques are being utilized for an upcoming invited manuscript highlighting the impact of elastin insufficiency on pulmonary vasculature with and without therapeutic intervention. The ability to visualize both the proximal and distal vasculature simultaneously and in 3D allowed us to see complex changes to the caliber, density, and tortuosity of the vasculature that would have been difficult to appreciate by histology or more traditional CT angiogram. In addition to this technique, were using advanced in-vivo ultrasound techniques to evaluate both vascular function and cardiac changes in the vasculature of aged elastin haploinsufficient mice. Collaborative efforts have yielded a JCI Insight paper for work on EPAS1 mutations showing developmental vascular malformations. We also contributed our expertise to show the utility of X-Ray Tomosynthesis, coupled with traditional histopathology, for guided sectioning (Journal of Microscopy). Weve employed more traditional vascular physiology techniques to explore cardiovascular phenotypes in a model of maternal loss of imprinting at the H19/IGF2 locus associated with Beckwith-Wiedemann syndrome). This work, recently published in eLife Sciences, highlighted the differential effects of increased IGF2 (cardiac hypertrophy and hyperplasia) and reduced H19 (progressive fibrosis and reduced cardiac function) . A mouse model of creatine transporter deficiency was also investigated with our team's guidance. The study found cardiac dysfunction and electrophysiologic changes in Slc6a8-/y mice (Genet Med). Currently, we are completing work with collaborators at Northwestern on a manuscript that utilizes our imaging and vascular physiology modalities to investigate novel mechanisms associated with Notch3 loss of function. Recently, a collaborative U01 was awarded under which future work in this model will be reported. Over the next year, we intend to expand both our CT and 3D murine MRI footprint while continuing to explore novel physiological methods. Of particular interest is the incorporation of new compounds that improve visualization and quantification of the arterial wall in in vivo mouse studies. Those studies were delayed both due to decreased in person effort allowable as a result of COVID restrictions and due to the quenching of the main magnet involved in our MRI studies.