Non-invasive ultrasound-based cardiovascular imaging in mouse models of atherosclerosis

Abstract

Atherosclerosis is a chronic multi-factorial vascular disease. It generally requires large clinical settings and over many years to study the disease progression in man. Genetically modified mouse models of atherosclerosis have dramatically increased research feasibility within this area. However, for optimal translational studies, it is increasingly important to explore how human-like these atherosclerotic mouse models demonstrate their disease phenotype and respond to established cardiovascular interventions.

The aims of this thesis were to develop and apply in vivo translational techniques to study living atherosclerotic mice, with human-relevant disease phenotype.

Color Doppler guided echocardiography and a high-frequency ultrasound biomicroscope were used for imaging of peripheral and coronary artery function and morphology. The potential role of IL-18 in mice was explored in relationship to mouse coronary artery disease. Finally temporal effects of rosuvastatin on cardiovascular phenotype were studied in an ApoE knockout mouse model of atherosclerosis.

This thesis illustrates that it is possible to investigate both central and peripheral atherosclerosis in living mice using ultrasound-based techniques. Our findings may also suggest an important role of IL-18 in late stage atherosclerosis in an advanced model of atherosclerosis. Finally, this particular ApoE knockout mouse model showed time-dependent beneficial cardiovascular effects following rosuvastatin treatment.

The established translational functional and morphological imaging platform in combination with our human-like statin-responding mouse model, provide us with powerful tools for future atherosclerosis research.