Objective-Hemodynamics plays a critical role in atherogenesis, but the association between flow pattern and preferential localization of lesion is not fully understood. We developed a mouse model of aortic valve regurgitation (AR) to change the aortic flow pattern and observed the effects on plaque formation. Methods and Results-High-frequency Doppler ultrasound imaging of 10 untreated C57BL/6J mice and 6 sham-treated low-density lipoprotein receptor-deficient (Ldlr Ϫ/Ϫ ) mice revealed consistent antegrade blood flow throughout the aorta and oscillatory flow only along the lesser curvature of the aortic arch. Catheter-induced AR in 7 Ldlr Ϫ/Ϫ mice produced various degrees of diastolic retrograde flow throughout the aorta. After the mice were fed a cholesterol-enriched diet for 6 weeks, the burden of atherosclerotic lesions was increased 6-fold, with the naturally plaque-resistant descending aorta becoming susceptible. The AR severity correlated positively with the lesion burden in the descending thoracic and abdominal aorta but negatively with the lesions in the ascending aorta and aortic arch. Key Words: atherosclerosis Ⅲ blood flow Ⅲ Doppler ultrasound Ⅲ genetically altered mice C omplex and disturbed blood flow at sites of aortic curvature, branches, bifurcations, or other arterial regions is a predisposing factor for atherosclerosis. 1,2 Endothelial cells of arteries sense wall shear stress (WSS), the frictional force of blood flow, and respond differently to various flow patterns by triggering unique signal transduction pathways that lead to distinct gene expression patterns. Unidirectional laminar WSS diminishes endothelial inflammatory responses and protects the artery from atherosclerosis. In contrast, low time-averaged WSS with oscillating directions correlates with increased predisposition to atherosclerosis. 3,4 However, the association between flow dynamics and atherogenesis is still not fully understood, and the roles of low WSS and oscillatory WSS have never been differentiated. Useful insights have been gained from previous studies on animals of various species by altering the blood flow through a variety of surgical interventions. 4 However, those models focus on specific aspects of endothelial cell biology in limited vessel segments and are unable to provide, at the systemic level, an in vivo environment with flow alteration in a morphologically normal aortic system for a comprehensive elucidation of the flow-plaque relationship.
Conclusion-ThisIn the last decade, mice have commonly been used in biological research because this species is most amenable to genetic manipulation. Low-density lipoprotein receptor-deficient (Ldlr Ϫ/Ϫ ) and apolipoprotein E-deficient (Apoe Ϫ/Ϫ ) mice are the most popular strains for studies related to atherosclerosis. 5-9 A model was developed by placing a cast around the common carotid artery of Apoe Ϫ/Ϫ mice, in an attempt to induce 3 regions of lowered, increased, and oscillatory WSS. 10,11 The segment facing elevated WSS was spared from lesions. However, the proxi...